Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy,leading to reduced quality of life and survival.For instance,irinotecan(CPT-11)usually causes severe gastrointestinal toxicity,with a...Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy,leading to reduced quality of life and survival.For instance,irinotecan(CPT-11)usually causes severe gastrointestinal toxicity,with a lack of effective therapeutic interventions,making treatment often unsustainable.Therefore,development of an effective and safe therapy is crucial for improving chemotherapy efficacy and the patients’quality of life.In this work,we developed a novel approach involving the helical-shaped cyanobacterium microalgae,Spirulina platensis(SP),to carry the bornyl acetate(BA)-loaded chitosan nanoparticles to enhance drug retention in the small intestine.We demonstrated the protection effect of BA against chemotherapy-induced intestinal injury using an epithelial cell model.In a mouse model,orally administered BA-ChNPs@SP accumulated in the small intestine and attenuated inflammation by reducing dsDNA release and oxidative stress.This was concomitant with the restoration of the intestinal barrier and modulation of the immune microenvironment.This work suggests the promise of the microalgae-carrying nanomedicine strategy for treatment of intestinal diseases,emphasizing its potential in addressing chemotherapy-induced gastrointestinal complications.展开更多
This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a ...This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a general part covering the grand lines and more in-depth views of more recent tannin,lignin,carbohydrate and soy bioadhesives,somemix of the other bio raw materials with soy protein and soy flour and some other differently sourced bioadhesives for wood,this review presents a more in-depth part on starch-based wood adhesives and a more indepth part covering plant protein-based adhesives.It must be kept in mind that the review is focused on completely or almost completely biosourced adhesives,the fashionable adhesives derived from mixes of biosourced materials with synthetic resins having been intentionally excluded.This choice was made as the latter constitute only an intermediate interval,possibly temporary if even for a somewhat long times,towards a final full bioeconomy of scale in this field.This review also focuses on more recent results,mainly obtained in the last 10–20 years,thus on adhesive formulations really innovative and sometimes even non-traditional.In all these fields there is still a lot of possibility of innovation for relevant formulation as this field is still in rapid growth.展开更多
The increase in wood and wood-based products in the construction and furniture sectors has grown exponentially,generating severe environmental and socioeconomic impacts.Particleboard panels have been the main cost-ben...The increase in wood and wood-based products in the construction and furniture sectors has grown exponentially,generating severe environmental and socioeconomic impacts.Particleboard panels have been the main cost-benefit option on the market due to their lightness and lower cost compared to solid wood.However,the synthetic adhesives used in producing traditional particleboard panels cause serious harm to human health.Developing particleboard panels with fibrous waste and natural adhesives could be a sustainable alternative for these sectors.The work aimed to create particleboards with fibrous wastes from the pseudostem of the banana tree(Musa paradisiaca)and different proportions of the natural adhesive cassava starch-CS in replacement of synthetic adhesive urea-formaldehyde-UF.Five experimental groups were manufactured with banana trees and different percentages of UF and CS adhesives,namely(100UF–0%CS),(50%UF–50%CS),(30%UF–70%CS),(10%UF–90%CS)and(0%UF–100%CS).The particleboards had their physical-mechanical properties determined.The apparent density values did not show significant variation between the assessed treatments.Regarding the water absorption and thickness swelling,the best performances were observed for the panels made without the addition of CS(100%UF).For the mechanical properties of static bending strength and Janka hardness,it was identified that adding up to 50%CS did not interfere with the quality of the panels.These analyses show that the particleboard panels produced with wastes of the banana tree bonded with natural CS adhesivemay be an economically viable and environmentally correct alternative,positively strengthening the development of sustainable strategies.展开更多
Bioadhesive polymers can serve as surgical sealants with a wide range of potential clinical applications, including augmentation of wound closure and acute induction of hemostasis. Key determinants of sealant efficacy...Bioadhesive polymers can serve as surgical sealants with a wide range of potential clinical applications, including augmentation of wound closure and acute induction of hemostasis. Key determinants of sealant efficacy include the strength and duration of tissue-material adhesion, as well as material biocompatibility. Canonical bioadhesive materials, however, are limited by a tradeoff among performance criteria that is largely governed by the efficiency of tissue-material interactions. In general, increasingly bioreactive materials are endowed with greater bioadhesive potential and protracted residence time, but incite more tissue damage and localized inflammation. One emergent strategy to improve sealant clinical performance is application-specific material design, with the goal of leveraging both local soft tissue surface chemistry and environmental factors to promote adhesive tissue-material interactions. We hypothesize that copolymer systems with equivalent bioreactive group densities (isoreactive) but different amounts/oxidation states of constituent polymers will exhibit differential interactions across soft tissue types. We synthesized an isoreactive family of aldehyde-mediated co-polymers, and subjected these materials to physical (gelation time), mechanical (bulk modulus and adhesion strength), and biological (in-vitro cytotoxicity and in-vivo biocompatibility) assays indicative of sealant performance. Results show that while bioadhesion to a range of soft tissue surfaces (porcine aortic adventitia, renal artery adventitia, renal cortex, and pericardium) varies with isoreactive manipulation, general indicators of material biocompatibility remain constant. Together these findings suggest that isore-active tuning of polymeric systems is a promising strategy to circumvent current challenges in surgical sealant applications.展开更多
<strong>Background:</strong> This work evaluated the capacity of a dry emulsion as a carrier of viable microorganisms with potential use as prophylaxis of infectious diseases. <strong>Methods:</st...<strong>Background:</strong> This work evaluated the capacity of a dry emulsion as a carrier of viable microorganisms with potential use as prophylaxis of infectious diseases. <strong>Methods:</strong> The aqueous phase containing <em>P. multocida </em>not viable in PBS was emulsified in mineral oil to obtain a w/o emulsion. The microorganisms remained stable and only in two cases (n = 6) did the bacterial concentration decrease. Scanning Electron Microscopy (SEM) revealed a structure of a system with the organized association of particles with cubic symmetry. Using two <em>ex vivo </em>bioadhesion systems, it was demonstrated that the disperse-adsorbed system is capable of adhering to the intestinal mucosa and remains adhered for long periods of time. <strong>Results: </strong>The no viability of the bacteria in the dry emulsion and the possibility of controlled release were confirmed. <em>In vivo </em>trial was conducted in pigs. It was possible to locate the emulsion and the bacteria attached to the gut of the living animal. An ELISA kit was used to monitor the mean antibody titer of treated pigs over a 2-week period, and a classic primary response curve occurred when the titer was plotted against time. <strong>Conclusion: </strong>We propose the disperse-adsorbed system as an alternative to commonly used vehicles for immunogens in the oral vaccines.展开更多
Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gast...Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections.展开更多
Gatifloxacin eye drops are frequently used in eye infections.However such formulations have a major drawback i.e.short duration of action and usually require 4e6 times installations daily.A chitosan coated niosomal fo...Gatifloxacin eye drops are frequently used in eye infections.However such formulations have a major drawback i.e.short duration of action and usually require 4e6 times installations daily.A chitosan coated niosomal formulation of gatifloxain was purposed to show a longer retention time on eyes and subsequent reduction in dosing frequency.Vesicles were prepared by solvent injection method using cholesterol and Span-60.An extensive optimization of formulation was done using different ratios of cholesterol,Span-60 and drug,revealed NS60-5(cholesterol:span-6050:50 and drug content of 20 mg)to be the optimized niosome formulation.NS60-5 had shown a highest entrapment efficiency of 64.9±0.66%with particle size 213.2±1.5 nm and zeta potential34.7±2.2 mV.Optimized niosomes were also coated with different concentrations of chitosan and evaluated.Permeation studies had revealed that optimized niosomes(86.77±1.31%)had increased the transcorneal permeation of Gatifloxacin more than two fold than simple drug solution(37.19±1.1%).Longer retention potential of the coated niosomes was further verified by fluorescence microscopy.Study revealed that simple dye solution got easily washed out with in 6 h.The uncoated niosomes(NS60-5)showed a longer retention(more than 6 h),which was further enhanced in case of coated niosomes i.e.CNS60-1(more than 12 h).Antimicrobial studies had shown the better efficacy of CNS60-1(zone of inhibition)when compared to marketed formulation.The final chitosan formulation was found to have shown better ocular tolerability as demonstrated by corneal hydration test histopathology investigations.展开更多
Polycarbophil(PCP),a kind of pharmaceutical polymers with superior bioadhesive properties has been widely used in the field of controlled drug delivery systems.It could be used as a highly efficient thickener,bioadhe...Polycarbophil(PCP),a kind of pharmaceutical polymers with superior bioadhesive properties has been widely used in the field of controlled drug delivery systems.It could be used as a highly efficient thickener,bioadhesive agent,suspending aid and emulsion stabilizer when dispersed in water or other polar solvents.These exceptional utilities of the polymers result from their hydrophilic nature.Hydrogen bonding plays an important role in most adhesion behaviours and becomes the main adhesion force.This paper reviews the applications of PCP in pharmacy over the past decades,and clarifies its unique advantages in the bioadhesive formulations.After an introduction discussing its structural characteristics and action mechanism,the focus turned to the description of its available applications in detail with particular emphasis on the ocular,nasal,vagina and oral drug delivery systems.The other less developed formulations are also described,including the buccal and the transdermal delivery systems.展开更多
A high performance composite membrane was prepared under the inspiration of bioadhesion principles for pervaporative dehydration of ethanol.Chitosan(CS)and polyacrylonitrile(PAN)ultrafiltration membranes were used as ...A high performance composite membrane was prepared under the inspiration of bioadhesion principles for pervaporative dehydration of ethanol.Chitosan(CS)and polyacrylonitrile(PAN)ultrafiltration membranes were used as the active layer and the support layer,respectively.Guar gum(GG),a natural bioadhesive,was introduced as the intermediate bonding layer to improve the separation performance and stability of the fabricated CS/GG/PAN composite membranes.The contact angle of the GG layer was just between those of the CS layer and the PAN layer,minimizing the difference of hydrophilicity between the active layer and the support layer.The peeling strength of the composite membrane was significantly enhanced after the introduction of the GG layer.The effects of preparation conditions and operation conditions including GG concentration,operating temperature and ethanol concentration in feed on the pervaporation performance were investigated.The as-fabricated CS/GG/PAN composite membrane showed the optimum performance with a permeation flux of up to804 g·m-2·h-1and a separation factor higher than 1900.Besides,the composite membranes exhibited a desirable long-term operational stability.展开更多
Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging.Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies,makin...Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging.Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies,making tissue bridging challenging.Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles(ACPs) made from chitosan,acrylic acid,1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC) and N-hydroxysuccinimide(NHS).The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart,intestine,liver,muscle,and stomach.Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells(LO2)and human intestinal epithelial cells(Caco-2).The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models.The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart,liver,and kidney as the ex vivo models.Furthermore,a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness,biocompatibility,and applicability in clinical surgery.Results ACPs are applicable to confined and irregular tissue defects,such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs.ACPs formed tough adhesion between tissues[(670.9±50.1) J/m^(2) for the heart,(607.6±30.0) J/m^(2) for the intestine,(473.7±37.0) J/m^(2) for the liver,(186.1±13.3) J/m^(2) for the muscle,and(579.3±32.3) J/m^(2) for the stomach].ACPs showed considerable cytocompatibility in vitro study,with a high level of cell viability for 3 d[(98.8±1.2)%for LO2 and(98.3±1.6)%for Caco-2].It has comparable inflammation repair in a ruptured rat liver(P=0.58 compared with suture closure),the same with intestinal anastomosis in rabbits(P=0.40 compared with suture anastomosis).Additionally,ACP-based intestinal anastomosis(less than 30 s) was remarkably faster than the conventional suturing process(more than 10 min).When ACPs degrade after surgery,the tissues heal across the adhesion interface.Conclusions ACPs are promising as the adhesive for clinical operations and battlefield rescue,with the capability to bridge irregular tissue defects rapidly.展开更多
Restorative materials in the new era aim to be “bio-active” and long-lasting. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and wound...Restorative materials in the new era aim to be “bio-active” and long-lasting. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and wound healing, we design and evaluate several novel chitosan-vitamin C (5:1) containing hydrogels as a prototype of host:vip molecular free radical defense material containing hydroethanoic propolis extract (antioxidant containing material), naproxen, ibuprofen (non steroidal anti-inflammatory medication), or aspirin (pain relieve medication and free radical scavengers) as functional restorative materials. We will evaluate the physical properties, bonding to dentin as well as test the bioadhesion of the newly designed materials in order to access the suitability of these prototype materials as suitable restorative materials. Materials and Methods: The hydrogels were prepared by previously reported by us protocol. The physico-chemical features including surface morphology (SEM), release behaviors, stability of the therapeutic agent-anti-oxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel were reported. Bio-adhesive studies were performed in order to assess the suitability of these designed materials. Results: Release of aspirin, ibuprofen and naproxen conferred the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Either the release of therapeutic agents or the antioxidant stability was affected by storage over a 12-month period. All chitosan:vitamin C hydrogels showed gave significantly higher shear bond values than dentin treated or not treated with phosphoric acid, which highlighted the feasibility. The bio-adhesive capacity of the materials in the 2 separate “in vitro” systems were tested and quantified. Additional action of chitosan:vitamin C pre-complex was investigated and it was found that favourable synergistic effect of free radical build-in defense mechanism of the new functional materials. Conclusion: Additional action of chitosan:vitamin C pre-complex was investigated and it was found that favorable synergistic effect of free radical build-in defense mechanism of the new functional materials, increased dentin bond strength, sustainable bio-adhesion, and acted as a “proof of concept” for the functional multi-dimensional restorative materials with potential application in wound healing in vitro.展开更多
In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies an...In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies and in vitro mucoadhesion test were performed. High molecular weight grades of KlucelTM hydroxypropylcellulose were used as a thermoplastic polymer. TEC and PEG 400 were chosen as plasticizer. According to the obtained results of melt viscosity measurements, the maximum torque of extrudates prepared using PEG 400 increased with increasing drug loading. The thermo-gravimetric analyses showed that natamycin is stable up to 198℃ and this result gives the opportunity to hot melt extrussion process at 90℃. In vitro drug release results showed that the release was extended up to 72 hours and drug release rate increased with increasing drug loading. In respect to the in vitro mucoadhesion test results, the values of work of mucoadhesion were found high as 771,977 mN.mm, 753,199 mN.mm, 686,356 mN.mm for the prepared hot melt extruded mini-matrices. Our results showed that the developed formulations were found worthy of further studies.展开更多
Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility.However,they often face limitations due to the uncontrollable phase transition of gel...Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility.However,they often face limitations due to the uncontrollable phase transition of gelatin,which is dominated by hydrogen bonds between peptide chains.Here,we developed controllable phase transition gelatin-based(CPTG)bioadhesives by regulating the dynamic balance of hydrogen bonds between the peptide chains using 2-hydroxyethylurea(HU)and punicalagin(PA).These CPTG bioadhesives exhibited significant enhancements in adhesion energy and injectability even at 4℃compared to traditional gelatin bioadhesives.The developed bioadhesives could achieve self-reinforcing interfacial adhesion upon contact with moist wound tissues.This effect was attributed to HU diffusion,which disrupted the dynamic balance of hydrogen bonds and therefore induced a localized structural densification.This process was further facilitated by the presence of pyrogallol from PA.Furthermore,the CPTG bioadhesive could modulate the immune microenvironment,offering antibacterial,antioxidant,and immune-adjustable properties,thereby accelerating diabetic wound healing,as confirmed in a diabetic wound rat model.This proposed design strategy is not only crucial for developing controllable phase-transition bioadhesives for diverse applications,but also paves the way for broadening the potential applications of gelatin-based biomaterials.展开更多
Repairing Achilles tendon has emerged as a long-standing challenge in the orthopaedic surgeries.Although suture is the gold standard for re-attaching and repairing the fractured Achilles tendons in clinical surgeries,...Repairing Achilles tendon has emerged as a long-standing challenge in the orthopaedic surgeries.Although suture is the gold standard for re-attaching and repairing the fractured Achilles tendons in clinical surgeries,it is still subjected to numerous adverse side-effects,including chronic inflammatory,tendon tissue re-rupture,scar formation,and post-surgical peritendinous adhesion.In this work,we develop a class of hydrogel bioadhesives with tailored nanoscale phase separation for Achilles tendon repairing.To address the existing limitations of sutures,our hydrogel bioadhesives encompass three core functionalities:(i)instant and tough adhesion to Achilles tendon tissues,(ii)extraordinary long-term adhesion robustness under wet and dynamic in vivo conditions,and(iii)anti-postsurgical peritendinous adhesion.Combining our hydrogel bioadhesives with sutures,such kind of integrated approach enables a conformable yet robust biointerface with the tendon tissues,and prevents the fibroblast migration and formation of connective tissues,thus facilitating the tendon repairing.The hydrogel bioadhesives reported here open up new opportunities for the repairing of fractured Achilles tendons in diverse and complicated clinical scenarios.展开更多
Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel tha...Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel that possesses rapid gelation,firm tissue adhesion,high mechanical strength,suitable degradability,and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets.Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing.In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy,wound closure,alveolar ridge preservation,and in situ alveolar bone regeneration.Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation,elevated collagen deposition,higher osteoblast activity,and enhanced angiogenesis.Together,our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.展开更多
Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the p...Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer.Herein,we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy.The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin(DOX)formed by consecutive ultrasonication-inducedβ-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion,exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy,as well as simultaneous release of DOX to finally achieve effective anti-cancer effect.A stretchable bioadhesive is fabricated by copolymerization ofα-thioctic acid and N,N-diacryloyl-L-lysine,and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions.The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing.Ultimately,in vivo animal studies substantiate the efficacy of our methodology,wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.展开更多
Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis(UC).Here,inspire...Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis(UC).Here,inspired by sandcastle worm adhesives,we proposed a water-immiscible coacervate(EMNs-gel)with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles.Driven by intestinal peristalsis,the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion,resulting from matrix metalloproteinases(MMPs)-triggered release of Fe3+from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces.Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces,achieving highly effective hemostasis,and displaying an extended residence time(48 h).This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC,showcasing great potential for clinical applications.展开更多
The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release.It consists of a drug loaded polymeric film made up of a bilayer of immediate(IR)and cont...The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release.It consists of a drug loaded polymeric film made up of a bilayer of immediate(IR)and controlled release(CR)layers folded into a hard gelatin capsule.Gast roretention results from unfolding and swelling of the film and its bioadhesion to the gastric.mucosa.Furosemide,a drug with a narrow absorption window,was selected as the model drug.Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol■ 971P NF in the CR layer of the bilayer film resulted in optimum drug release,bioadhesion and mechanical properties.The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drugover 1 hand CR for up to 12 h in acidic medium.X-ray diffraction,differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices.The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic wind ows.展开更多
Four kinds of poly（ethylene glycol） （PEG） derivatives with the similar backbone and different side groups have been synthesized successfully. When both catecholamine and double bond are tethered to polymer backbon...Four kinds of poly（ethylene glycol） （PEG） derivatives with the similar backbone and different side groups have been synthesized successfully. When both catecholamine and double bond are tethered to polymer backbone, i.e., the PEG backbone, simultaneously, the polymer can accelerate the curing speed of ethyl a-cyanoacrylate （commer- cially available as 502） greatly under the same conditions （the curing time of such system is no more than 5 s）. Probably this is due to the autoxidation of catecholamines. Through the redox-cycling, catecholamines can produce, collect free radicals, and thus initiate the free radical polymerization. Due to the fast-curing of such material when mixed with a-cyanoacrylate, we could design and develop a new bicomponent super bioglue used in the dentistry or other bioenvironment requiring super fast settlement for further surgical operations.展开更多
The high demand for rapid wound healing has spurred the development of multifunctional and smart bioadhesives with strong bioadhesion,antibacterial effect,real-time sensing,wireless communication,and on-demand treatme...The high demand for rapid wound healing has spurred the development of multifunctional and smart bioadhesives with strong bioadhesion,antibacterial effect,real-time sensing,wireless communication,and on-demand treatment capabilities.Bioadhesives with bio-inspired structures and chemicals have shown unprecedented adhesion strengths,as well as tunable optical,electrical,and bio-dissolvable properties.Accelerated wound healing has been achieved via directly released antibacterial and growth factors,material or drug-induced host immune responses,and delivery of curative cells.Most recently,the integration of biosensing and treatment modules with wireless units in a closed-loop system yielded smart bioadhesives,allowing real-time sensing of the physiological conditions(e.g.,pH,temperature,uric acid,glucose,and cytokine)with iterative feedback for drastically enhanced,stage-specific wound healing by triggering drug delivery and treatment to avoid infection or prolonged inflammation.Despite rapid advances in the burgeoning field,challenges still exist in the design and fabrication of integrated systems,particularly for chronic wounds,presenting significant opportunities for the future development of next-generation smart materials and systems.展开更多
基金the National Key Research and Development Program of China(2022YFE0203600,China)NFSC(81925035,82341232)+2 种基金Program of Shanghai Committee of Science and Technology(21ZR1475200,China)Department of Science and Technology of Guangdong Province(High-Level R&D and Innovative Research Institute 2021B0909050003)SciTech Projects of Zhongshan(CXTD2022011,LJ2021001).
文摘Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy,leading to reduced quality of life and survival.For instance,irinotecan(CPT-11)usually causes severe gastrointestinal toxicity,with a lack of effective therapeutic interventions,making treatment often unsustainable.Therefore,development of an effective and safe therapy is crucial for improving chemotherapy efficacy and the patients’quality of life.In this work,we developed a novel approach involving the helical-shaped cyanobacterium microalgae,Spirulina platensis(SP),to carry the bornyl acetate(BA)-loaded chitosan nanoparticles to enhance drug retention in the small intestine.We demonstrated the protection effect of BA against chemotherapy-induced intestinal injury using an epithelial cell model.In a mouse model,orally administered BA-ChNPs@SP accumulated in the small intestine and attenuated inflammation by reducing dsDNA release and oxidative stress.This was concomitant with the restoration of the intestinal barrier and modulation of the immune microenvironment.This work suggests the promise of the microalgae-carrying nanomedicine strategy for treatment of intestinal diseases,emphasizing its potential in addressing chemotherapy-induced gastrointestinal complications.
文摘This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a general part covering the grand lines and more in-depth views of more recent tannin,lignin,carbohydrate and soy bioadhesives,somemix of the other bio raw materials with soy protein and soy flour and some other differently sourced bioadhesives for wood,this review presents a more in-depth part on starch-based wood adhesives and a more indepth part covering plant protein-based adhesives.It must be kept in mind that the review is focused on completely or almost completely biosourced adhesives,the fashionable adhesives derived from mixes of biosourced materials with synthetic resins having been intentionally excluded.This choice was made as the latter constitute only an intermediate interval,possibly temporary if even for a somewhat long times,towards a final full bioeconomy of scale in this field.This review also focuses on more recent results,mainly obtained in the last 10–20 years,thus on adhesive formulations really innovative and sometimes even non-traditional.In all these fields there is still a lot of possibility of innovation for relevant formulation as this field is still in rapid growth.
基金financed by“Conselho Nacional de Desenvolvimento Cientifico e Tecnologico”(CNPq)and“Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior”(CAPES)-Finance Code 001.
文摘The increase in wood and wood-based products in the construction and furniture sectors has grown exponentially,generating severe environmental and socioeconomic impacts.Particleboard panels have been the main cost-benefit option on the market due to their lightness and lower cost compared to solid wood.However,the synthetic adhesives used in producing traditional particleboard panels cause serious harm to human health.Developing particleboard panels with fibrous waste and natural adhesives could be a sustainable alternative for these sectors.The work aimed to create particleboards with fibrous wastes from the pseudostem of the banana tree(Musa paradisiaca)and different proportions of the natural adhesive cassava starch-CS in replacement of synthetic adhesive urea-formaldehyde-UF.Five experimental groups were manufactured with banana trees and different percentages of UF and CS adhesives,namely(100UF–0%CS),(50%UF–50%CS),(30%UF–70%CS),(10%UF–90%CS)and(0%UF–100%CS).The particleboards had their physical-mechanical properties determined.The apparent density values did not show significant variation between the assessed treatments.Regarding the water absorption and thickness swelling,the best performances were observed for the panels made without the addition of CS(100%UF).For the mechanical properties of static bending strength and Janka hardness,it was identified that adding up to 50%CS did not interfere with the quality of the panels.These analyses show that the particleboard panels produced with wastes of the banana tree bonded with natural CS adhesivemay be an economically viable and environmentally correct alternative,positively strengthening the development of sustainable strategies.
文摘Bioadhesive polymers can serve as surgical sealants with a wide range of potential clinical applications, including augmentation of wound closure and acute induction of hemostasis. Key determinants of sealant efficacy include the strength and duration of tissue-material adhesion, as well as material biocompatibility. Canonical bioadhesive materials, however, are limited by a tradeoff among performance criteria that is largely governed by the efficiency of tissue-material interactions. In general, increasingly bioreactive materials are endowed with greater bioadhesive potential and protracted residence time, but incite more tissue damage and localized inflammation. One emergent strategy to improve sealant clinical performance is application-specific material design, with the goal of leveraging both local soft tissue surface chemistry and environmental factors to promote adhesive tissue-material interactions. We hypothesize that copolymer systems with equivalent bioreactive group densities (isoreactive) but different amounts/oxidation states of constituent polymers will exhibit differential interactions across soft tissue types. We synthesized an isoreactive family of aldehyde-mediated co-polymers, and subjected these materials to physical (gelation time), mechanical (bulk modulus and adhesion strength), and biological (in-vitro cytotoxicity and in-vivo biocompatibility) assays indicative of sealant performance. Results show that while bioadhesion to a range of soft tissue surfaces (porcine aortic adventitia, renal artery adventitia, renal cortex, and pericardium) varies with isoreactive manipulation, general indicators of material biocompatibility remain constant. Together these findings suggest that isore-active tuning of polymeric systems is a promising strategy to circumvent current challenges in surgical sealant applications.
文摘<strong>Background:</strong> This work evaluated the capacity of a dry emulsion as a carrier of viable microorganisms with potential use as prophylaxis of infectious diseases. <strong>Methods:</strong> The aqueous phase containing <em>P. multocida </em>not viable in PBS was emulsified in mineral oil to obtain a w/o emulsion. The microorganisms remained stable and only in two cases (n = 6) did the bacterial concentration decrease. Scanning Electron Microscopy (SEM) revealed a structure of a system with the organized association of particles with cubic symmetry. Using two <em>ex vivo </em>bioadhesion systems, it was demonstrated that the disperse-adsorbed system is capable of adhering to the intestinal mucosa and remains adhered for long periods of time. <strong>Results: </strong>The no viability of the bacteria in the dry emulsion and the possibility of controlled release were confirmed. <em>In vivo </em>trial was conducted in pigs. It was possible to locate the emulsion and the bacteria attached to the gut of the living animal. An ELISA kit was used to monitor the mean antibody titer of treated pigs over a 2-week period, and a classic primary response curve occurred when the titer was plotted against time. <strong>Conclusion: </strong>We propose the disperse-adsorbed system as an alternative to commonly used vehicles for immunogens in the oral vaccines.
文摘Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections.
文摘Gatifloxacin eye drops are frequently used in eye infections.However such formulations have a major drawback i.e.short duration of action and usually require 4e6 times installations daily.A chitosan coated niosomal formulation of gatifloxain was purposed to show a longer retention time on eyes and subsequent reduction in dosing frequency.Vesicles were prepared by solvent injection method using cholesterol and Span-60.An extensive optimization of formulation was done using different ratios of cholesterol,Span-60 and drug,revealed NS60-5(cholesterol:span-6050:50 and drug content of 20 mg)to be the optimized niosome formulation.NS60-5 had shown a highest entrapment efficiency of 64.9±0.66%with particle size 213.2±1.5 nm and zeta potential34.7±2.2 mV.Optimized niosomes were also coated with different concentrations of chitosan and evaluated.Permeation studies had revealed that optimized niosomes(86.77±1.31%)had increased the transcorneal permeation of Gatifloxacin more than two fold than simple drug solution(37.19±1.1%).Longer retention potential of the coated niosomes was further verified by fluorescence microscopy.Study revealed that simple dye solution got easily washed out with in 6 h.The uncoated niosomes(NS60-5)showed a longer retention(more than 6 h),which was further enhanced in case of coated niosomes i.e.CNS60-1(more than 12 h).Antimicrobial studies had shown the better efficacy of CNS60-1(zone of inhibition)when compared to marketed formulation.The final chitosan formulation was found to have shown better ocular tolerability as demonstrated by corneal hydration test histopathology investigations.
基金the work was supported by a research group from Shenyang Pharmaceutical University,including the financial support.And get the vigorous help from all the teachers and students of Pharmacy Department.
文摘Polycarbophil(PCP),a kind of pharmaceutical polymers with superior bioadhesive properties has been widely used in the field of controlled drug delivery systems.It could be used as a highly efficient thickener,bioadhesive agent,suspending aid and emulsion stabilizer when dispersed in water or other polar solvents.These exceptional utilities of the polymers result from their hydrophilic nature.Hydrogen bonding plays an important role in most adhesion behaviours and becomes the main adhesion force.This paper reviews the applications of PCP in pharmacy over the past decades,and clarifies its unique advantages in the bioadhesive formulations.After an introduction discussing its structural characteristics and action mechanism,the focus turned to the description of its available applications in detail with particular emphasis on the ocular,nasal,vagina and oral drug delivery systems.The other less developed formulations are also described,including the buccal and the transdermal delivery systems.
基金Supported by the New Century Excellent Talents in University(NCET-10-0623)the National Natural Science Foundation for Distinguished Young Scholars(21125627)+1 种基金the National Basic Research Program of China(2009CB623404)State Key Laboratory for Modification of Chemical Fibers and Polymer Materials(Dong Hua University)
文摘A high performance composite membrane was prepared under the inspiration of bioadhesion principles for pervaporative dehydration of ethanol.Chitosan(CS)and polyacrylonitrile(PAN)ultrafiltration membranes were used as the active layer and the support layer,respectively.Guar gum(GG),a natural bioadhesive,was introduced as the intermediate bonding layer to improve the separation performance and stability of the fabricated CS/GG/PAN composite membranes.The contact angle of the GG layer was just between those of the CS layer and the PAN layer,minimizing the difference of hydrophilicity between the active layer and the support layer.The peeling strength of the composite membrane was significantly enhanced after the introduction of the GG layer.The effects of preparation conditions and operation conditions including GG concentration,operating temperature and ethanol concentration in feed on the pervaporation performance were investigated.The as-fabricated CS/GG/PAN composite membrane showed the optimum performance with a permeation flux of up to804 g·m-2·h-1and a separation factor higher than 1900.Besides,the composite membranes exhibited a desirable long-term operational stability.
基金supported by the National Natural Science Foundation of China (12102388, T2125009, 92048302)the National Key Research and Development Program of China 2017 (YFA0701100)the Fundamental Research Funds for the Central Universities (226-2022-00141, 2022QZJH52)。
文摘Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging.Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies,making tissue bridging challenging.Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles(ACPs) made from chitosan,acrylic acid,1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC) and N-hydroxysuccinimide(NHS).The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart,intestine,liver,muscle,and stomach.Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells(LO2)and human intestinal epithelial cells(Caco-2).The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models.The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart,liver,and kidney as the ex vivo models.Furthermore,a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness,biocompatibility,and applicability in clinical surgery.Results ACPs are applicable to confined and irregular tissue defects,such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs.ACPs formed tough adhesion between tissues[(670.9±50.1) J/m^(2) for the heart,(607.6±30.0) J/m^(2) for the intestine,(473.7±37.0) J/m^(2) for the liver,(186.1±13.3) J/m^(2) for the muscle,and(579.3±32.3) J/m^(2) for the stomach].ACPs showed considerable cytocompatibility in vitro study,with a high level of cell viability for 3 d[(98.8±1.2)%for LO2 and(98.3±1.6)%for Caco-2].It has comparable inflammation repair in a ruptured rat liver(P=0.58 compared with suture closure),the same with intestinal anastomosis in rabbits(P=0.40 compared with suture anastomosis).Additionally,ACP-based intestinal anastomosis(less than 30 s) was remarkably faster than the conventional suturing process(more than 10 min).When ACPs degrade after surgery,the tissues heal across the adhesion interface.Conclusions ACPs are promising as the adhesive for clinical operations and battlefield rescue,with the capability to bridge irregular tissue defects rapidly.
文摘Restorative materials in the new era aim to be “bio-active” and long-lasting. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and wound healing, we design and evaluate several novel chitosan-vitamin C (5:1) containing hydrogels as a prototype of host:vip molecular free radical defense material containing hydroethanoic propolis extract (antioxidant containing material), naproxen, ibuprofen (non steroidal anti-inflammatory medication), or aspirin (pain relieve medication and free radical scavengers) as functional restorative materials. We will evaluate the physical properties, bonding to dentin as well as test the bioadhesion of the newly designed materials in order to access the suitability of these prototype materials as suitable restorative materials. Materials and Methods: The hydrogels were prepared by previously reported by us protocol. The physico-chemical features including surface morphology (SEM), release behaviors, stability of the therapeutic agent-anti-oxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel were reported. Bio-adhesive studies were performed in order to assess the suitability of these designed materials. Results: Release of aspirin, ibuprofen and naproxen conferred the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Either the release of therapeutic agents or the antioxidant stability was affected by storage over a 12-month period. All chitosan:vitamin C hydrogels showed gave significantly higher shear bond values than dentin treated or not treated with phosphoric acid, which highlighted the feasibility. The bio-adhesive capacity of the materials in the 2 separate “in vitro” systems were tested and quantified. Additional action of chitosan:vitamin C pre-complex was investigated and it was found that favourable synergistic effect of free radical build-in defense mechanism of the new functional materials. Conclusion: Additional action of chitosan:vitamin C pre-complex was investigated and it was found that favorable synergistic effect of free radical build-in defense mechanism of the new functional materials, increased dentin bond strength, sustainable bio-adhesion, and acted as a “proof of concept” for the functional multi-dimensional restorative materials with potential application in wound healing in vitro.
基金The authors would like to thank to Scientific and Technological Research Council of Turkey(TUBITAK)(115S476)for their supportThe authors also would like to thank to Pharmaceutical Sciences Research Centre(FABAL)for their support.
文摘In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies and in vitro mucoadhesion test were performed. High molecular weight grades of KlucelTM hydroxypropylcellulose were used as a thermoplastic polymer. TEC and PEG 400 were chosen as plasticizer. According to the obtained results of melt viscosity measurements, the maximum torque of extrudates prepared using PEG 400 increased with increasing drug loading. The thermo-gravimetric analyses showed that natamycin is stable up to 198℃ and this result gives the opportunity to hot melt extrussion process at 90℃. In vitro drug release results showed that the release was extended up to 72 hours and drug release rate increased with increasing drug loading. In respect to the in vitro mucoadhesion test results, the values of work of mucoadhesion were found high as 771,977 mN.mm, 753,199 mN.mm, 686,356 mN.mm for the prepared hot melt extruded mini-matrices. Our results showed that the developed formulations were found worthy of further studies.
基金supported by National Key Research and Development Program of China(grant nos.2021YFA1000200 and 2021YFA1000201)National Natural Science Foundation of China(grant nos.12372175,12102010 and 52363019)+1 种基金Tianjin Municipal Science and Technology Plan Project(grant no.24ZYCGSY00650)Tianjin Health Technology Project(grant no.TJWJ2022XK043).
文摘Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility.However,they often face limitations due to the uncontrollable phase transition of gelatin,which is dominated by hydrogen bonds between peptide chains.Here,we developed controllable phase transition gelatin-based(CPTG)bioadhesives by regulating the dynamic balance of hydrogen bonds between the peptide chains using 2-hydroxyethylurea(HU)and punicalagin(PA).These CPTG bioadhesives exhibited significant enhancements in adhesion energy and injectability even at 4℃compared to traditional gelatin bioadhesives.The developed bioadhesives could achieve self-reinforcing interfacial adhesion upon contact with moist wound tissues.This effect was attributed to HU diffusion,which disrupted the dynamic balance of hydrogen bonds and therefore induced a localized structural densification.This process was further facilitated by the presence of pyrogallol from PA.Furthermore,the CPTG bioadhesive could modulate the immune microenvironment,offering antibacterial,antioxidant,and immune-adjustable properties,thereby accelerating diabetic wound healing,as confirmed in a diabetic wound rat model.This proposed design strategy is not only crucial for developing controllable phase-transition bioadhesives for diverse applications,but also paves the way for broadening the potential applications of gelatin-based biomaterials.
基金support by Natural Science Foundation of Guangdong Province(Nos.2022A1515010152 and 2021A1515110735)the Basic Research Program of Shenzhen(Nos.JCYJ20210324105211032 and GJHZ20210705141809030)+1 种基金the Scientific Research Platforms and Projects of University of Guangdong Provincial Education Office(No.2022ZDZX3019)supported in part by the Science,Technology,and Innovation Commission of Shenzhen Municipality(No.ZDSYS20200811143601004).
文摘Repairing Achilles tendon has emerged as a long-standing challenge in the orthopaedic surgeries.Although suture is the gold standard for re-attaching and repairing the fractured Achilles tendons in clinical surgeries,it is still subjected to numerous adverse side-effects,including chronic inflammatory,tendon tissue re-rupture,scar formation,and post-surgical peritendinous adhesion.In this work,we develop a class of hydrogel bioadhesives with tailored nanoscale phase separation for Achilles tendon repairing.To address the existing limitations of sutures,our hydrogel bioadhesives encompass three core functionalities:(i)instant and tough adhesion to Achilles tendon tissues,(ii)extraordinary long-term adhesion robustness under wet and dynamic in vivo conditions,and(iii)anti-postsurgical peritendinous adhesion.Combining our hydrogel bioadhesives with sutures,such kind of integrated approach enables a conformable yet robust biointerface with the tendon tissues,and prevents the fibroblast migration and formation of connective tissues,thus facilitating the tendon repairing.The hydrogel bioadhesives reported here open up new opportunities for the repairing of fractured Achilles tendons in diverse and complicated clinical scenarios.
基金support for the work from the Ministry of Science and Technology of China (2020YFA0908900)National Natural Science Foundation of China (21935011 and 21725403)+2 种基金Shenzhen Science and Technology Innovation Commission (KQTD20200820113012029,JCYJ20190814114605162,and JCYJ20220818100601003)Guangdong Basic and Applied Basic Research Foundation (2022A1515110321)Guangdong Provincial Key Laboratory of Advanced Biomaterials (2022B1212010003).
文摘Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel that possesses rapid gelation,firm tissue adhesion,high mechanical strength,suitable degradability,and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets.Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing.In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy,wound closure,alveolar ridge preservation,and in situ alveolar bone regeneration.Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation,elevated collagen deposition,higher osteoblast activity,and enhanced angiogenesis.Together,our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.
基金support for this work from the National Natural Science Foundation of China(Grant No.52233008,51733006,32301120)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-042,2021-I2M-1-060)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2022-RC350-06).
文摘Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer.Herein,we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy.The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin(DOX)formed by consecutive ultrasonication-inducedβ-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion,exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy,as well as simultaneous release of DOX to finally achieve effective anti-cancer effect.A stretchable bioadhesive is fabricated by copolymerization ofα-thioctic acid and N,N-diacryloyl-L-lysine,and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions.The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing.Ultimately,in vivo animal studies substantiate the efficacy of our methodology,wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.
基金Chongqing Postdoctoral International Exchange Training Program(7820100997)Fundamental Research Funds for Central Universities(Nos.SWU-XDPY22010)+2 种基金National College Students Innovation and Entrepreneurship Training Program(202310635114)National Natural Science Foundation of China(No.81703424)Chongqing Graduate Student Research Innovation Project(CYB21121).
文摘Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis(UC).Here,inspired by sandcastle worm adhesives,we proposed a water-immiscible coacervate(EMNs-gel)with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles.Driven by intestinal peristalsis,the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion,resulting from matrix metalloproteinases(MMPs)-triggered release of Fe3+from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces.Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces,achieving highly effective hemostasis,and displaying an extended residence time(48 h).This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC,showcasing great potential for clinical applications.
文摘The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release.It consists of a drug loaded polymeric film made up of a bilayer of immediate(IR)and controlled release(CR)layers folded into a hard gelatin capsule.Gast roretention results from unfolding and swelling of the film and its bioadhesion to the gastric.mucosa.Furosemide,a drug with a narrow absorption window,was selected as the model drug.Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol■ 971P NF in the CR layer of the bilayer film resulted in optimum drug release,bioadhesion and mechanical properties.The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drugover 1 hand CR for up to 12 h in acidic medium.X-ray diffraction,differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices.The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic wind ows.
基金This work was supported by the National Natural Science Foundation of China （Nos. 50903096, 21134004）, the Department of Science Technology of Guangdong Province （No. 2008B090500196）, and the Fundamental Research Funds for the Central Universi- ties.
文摘Four kinds of poly（ethylene glycol） （PEG） derivatives with the similar backbone and different side groups have been synthesized successfully. When both catecholamine and double bond are tethered to polymer backbone, i.e., the PEG backbone, simultaneously, the polymer can accelerate the curing speed of ethyl a-cyanoacrylate （commer- cially available as 502） greatly under the same conditions （the curing time of such system is no more than 5 s）. Probably this is due to the autoxidation of catecholamines. Through the redox-cycling, catecholamines can produce, collect free radicals, and thus initiate the free radical polymerization. Due to the fast-curing of such material when mixed with a-cyanoacrylate, we could design and develop a new bicomponent super bioglue used in the dentistry or other bioenvironment requiring super fast settlement for further surgical operations.
基金supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award No.R21EB030140the National Heart,Lung,and Blood Institute of the National Institutes of Health under Award Number R61HL154215,the National Science Foundation(NSF)(Grant No.ECCS-1933072)Penn State University.Y.L.would like to acknowledge the support of the Natural Science Foundation of China under Grant 61825102,U21A20460.
文摘The high demand for rapid wound healing has spurred the development of multifunctional and smart bioadhesives with strong bioadhesion,antibacterial effect,real-time sensing,wireless communication,and on-demand treatment capabilities.Bioadhesives with bio-inspired structures and chemicals have shown unprecedented adhesion strengths,as well as tunable optical,electrical,and bio-dissolvable properties.Accelerated wound healing has been achieved via directly released antibacterial and growth factors,material or drug-induced host immune responses,and delivery of curative cells.Most recently,the integration of biosensing and treatment modules with wireless units in a closed-loop system yielded smart bioadhesives,allowing real-time sensing of the physiological conditions(e.g.,pH,temperature,uric acid,glucose,and cytokine)with iterative feedback for drastically enhanced,stage-specific wound healing by triggering drug delivery and treatment to avoid infection or prolonged inflammation.Despite rapid advances in the burgeoning field,challenges still exist in the design and fabrication of integrated systems,particularly for chronic wounds,presenting significant opportunities for the future development of next-generation smart materials and systems.
