Oseltamivir phosphate(OP),renowned as one of the most effective drugs for influenza treatment,encounters several challenges,including poor stability,difficulty in swallowing,and a bitter taste,thereby limiting its com...Oseltamivir phosphate(OP),renowned as one of the most effective drugs for influenza treatment,encounters several challenges,including poor stability,difficulty in swallowing,and a bitter taste,thereby limiting its compliance,particularly among children.Consequently,this study aimed to devise a novel sustained-release suspension of OP employing an ion exchange resin as a carrier to address these challenges.The OP-drug resin complex(OP-DRC)was synthesized utilizing ion exchange technology,while OP-coated microcapsules(OP-CM)were fabricated via the emulsion-evaporation method.The optimization of the formulation process for the OP sustained-release suspension was achieved through a combination of single-factor experimentation and orthogonal experimental design.Furthermore,the drug release kinetics and pharmacokinetic properties of the sustained-release suspension were thoroughly evaluated both in vitro and in vivo.Scanning electron microscopy(SEM),X-ray diffraction(XRD),and attenuated total reflectance Fourier-transform infrared spectroscopy(ATR-FTIR)analyses confirmed the formation of drug-resin complexes via ionic bonding.The in vitro cumulative release rates were found to be 16%(1 h),53%(6 h),and 84%(24 h),respectively.Notably,the self-made sustained-release suspension exhibited an extended half-life(21.518 h),delayed time to peak concentration(T_(max))(6 h),and reduced maximum plasma concentration(C_(max))(0.397μg/mL)in comparison to commercial granules(half-life=8.466 h;T_(max)=2 h;C_(max)=0.631μg/mL).Additionally,the area under the curve(AUC)indicated that the bioavailability of the self-made OP suspension surpassed that of the commercial OP granules by 101%.These findings underscored the successful development of an oral OP sustained-release suspension characterized by stability,tastelessness,ease of swallowing,convenient administration,and sustained-release properties,thereby potentially enhancing drug compliance among children.展开更多
Different dosage forms can significantly impact pharmacokinetics in vivo,leading to varied effects and potential adverse reactions.This study aimed to evaluate the efficacy,safety,and cost-effectiveness of isosorbide ...Different dosage forms can significantly impact pharmacokinetics in vivo,leading to varied effects and potential adverse reactions.This study aimed to evaluate the efficacy,safety,and cost-effectiveness of isosorbide mononitrate sustained-release capsules(IMSRC)combined with conventional treatments,compared to isosorbide mononitrate tablets(IMT)combined with conventional treatments,for managing angina pectoris in patients with coronary heart diseases.A network meta-analysis(NMA)was conducted to assess the efficacy and safety of IMSRC and IMT.Relevant literature was sourced from databases,including PubMed,Embase,Cochrane Library,ScienceDirect,Web of Science,CNKI,Wanfang,and VIP,covering publications up to July 2023.The cost-effectiveness analysis(CEA)was performed from the perspective of China’s healthcare system,utilizing inputs derived from the NMA.The analysis included 15 studies.The NMA results revealed no significant difference in efficacy and safety between IMSRC plus conventional treatments and IMT plus conventional treatments.However,both combinations were more effective than conventional treatments without isosorbide mononitrate.No differences in safety were observed among the three groups.The surface under the cumulative ranking(SUCRA)of the NMA indicated that IMT had a slight edge over IMSRC in the total effective rate of angina pectoris,whereas IMSRC showed higher probabilities for markedly effective rate and ECG effective rate compared to IMT.The incidence of adverse events was ranked as IMT>conventional preparation>IMSRC.The CEA results highlighted that the incremental cost-effectiveness ratios(ICERs)for the markedly effective and total effective rates of angina pectoris were-133.41 and-260.20,respectively.The ICERs for ECG effective rates were-83.34 and-234.24,respectively.In conclusion,while IMSRC combined with conventional treatments and IMT combined with conventional treatments were similar in efficacy and safety,IMSRC proved to be more economical.展开更多
Identification of chemical oxygen demand(COD)in municipal solid waste(MSW)landfill leachates is a challenging problem.This paper investigated the feasibility of using sodium persulfate(PS),a strong oxidant,as a permea...Identification of chemical oxygen demand(COD)in municipal solid waste(MSW)landfill leachates is a challenging problem.This paper investigated the feasibility of using sodium persulfate(PS),a strong oxidant,as a permeable reactive barrier(PRB)filling material.Firstly,sustained-release persulfate balls were manufactured to adjust the release rate of persulfate,the oxidation agent.In addition,Fe(II)-loaded activated carbon(Fe-AC)was used to help with an even distribution of Fe(II)in the porous medium(PRB in this case).Then,the oxidation efficiency and kinetic rate of COD removal by the sustained-release balls were subjected to batch tests.A mass ratio of 1:1.4:0.24:0.7 for PS:cement:sand:water was the most efficient for COD removal(95%).The breakthrough curve for a 5 mm sustained-release ball revealed that the retardation factor was 1.27 and that the hydrodynamic dispersion coefficient was 15.6 cm^(2)/d.The corresponding half-life of COD oxidation was 0.43 d,which was comparable with the half-life of PS release from sustained-release balls(0.56 d).The sustained-release persulfate balls were shown to be an economical material with a simple recipe and production method when catalyzed by Fe-AC.Compared with cutting-edge methods,sustained-release balls used in PRBs offer significant advantages in terms of both effectiveness and economy for the preparation of sustained-release and catalytic materials.These results verified the feasibility of using sustained-release persulfate balls as a PRB material for COD removal.展开更多
The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release...The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping test.With their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release kinetics.The structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic structures.Furthermore,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic preparations.Moreover,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%ethanol.In conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.展开更多
Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4....Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.展开更多
Aim To improve the dissolution rate and bioavailability of silybin. Methods Sustained-release silybin microspheres were prepared by the spherical crystallization technique with soliddispersing and release-retarding po...Aim To improve the dissolution rate and bioavailability of silybin. Methods Sustained-release silybin microspheres were prepared by the spherical crystallization technique with soliddispersing and release-retarding polymers. A differential scanning calorimeter and an X-ray diffractometer were used to investigate the dispersion state of silybin in the microspheres. The shape, surface morphology, and internal structure of the microspheres were observed using a scanning electron microscope. Characterization of the microspheres, such as average diameter, size distribution and bulk density of the microspheres was investigated. Results The particle size of the microspheres was determined mainly by the agitation speed. The dissolution rate of silybin from microspheres was enhanced by increasing the amount of the dispersing agents, and sustained by the retarding agents. The release rate of microspheres was controlled by adjusting the combination ratio of the dispersing agents to the retarding agents. The resuits of X-ray diffraction and differential scanning calorimetry analysis indicated that silybin was highly dispersed in the microspheres in amorphous state. The release profiles and content did not change after a three-month accelerated stability test at 40 ℃ and 75% relative humidity. Conclusion Sustained-release silybin microspheres with a solid dispersion structure were prepared successfully in one step by a spherical crystallization technique combined with solid dispersion technique. The preparation process is simple, reproducible and inexpensive. The method is efficient for designing sustained-release microspheres with water-insoluble drugs.展开更多
A qualitative and quantitative test method of fingerprint of Wuji gastric floating sustained-release tablets was established. High performance liquid chromatography （HPLC） was adopted, using Agilent ZORBAX SB-C18 co...A qualitative and quantitative test method of fingerprint of Wuji gastric floating sustained-release tablets was established. High performance liquid chromatography （HPLC） was adopted, using Agilent ZORBAX SB-C18 column （250 mm×4.6 mm, 5 μm） as the chromatographic column, and acetonitrile-0.05 mol/L potassium dihydrogen phosphate solution as the mobile phase in a gradient elution with the flow rate of 1.0 mL/min. Sample solution （10 μL） was injected and was tested at the wavelength of 225 nm for 75 min at the column temperature of 30 ℃, Fingerprint similarity software （2004A version） was used to conduct data analysis. A total of 11 batches of Wuji gastric floating sustained-release tablets were tested and analyzed with HPLC fingerprint. Seventeen common peaks were found and the similarity of the 11 batches of agents was greater than 0.9, indicating that the production process of the agent is stable and feasible. The method is operable and could effectively control the quality of Wuji gastric floating sustained-release tablets.展开更多
The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assay...The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.展开更多
This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagl...This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.展开更多
Rabbits with the body weight of （2.0 ± 0.5 ） kg were chosen, to study the effects of sustained-release calcium hydroxide and sustained-release hydro- chloric acid on nutrient digestion and absorption of rabbits...Rabbits with the body weight of （2.0 ± 0.5 ） kg were chosen, to study the effects of sustained-release calcium hydroxide and sustained-release hydro- chloric acid on nutrient digestion and absorption of rabbits. The results showed that sustained-release calcium hydroxide promoted digestion and absorption of nutri- ents, especially calcium and crude protein. The digestibility of calcium and crude protein was increased from 89.8% and 93.8% to 41.0% and 65.2%, respec- tively. Sustained-release hydrochloric acid was adverse to digestion and absorption of nutrients, especially calcium and crude protein. The digestibility of calcium and crude protein were decreased from 55.5% and 84.9% to 28.4% and 68.7%, respectively. The promotion effects of sustained-release hydrochloride on diges- tion lasted for 3 -4 d. Therefore, sustained-release calcium hydroxide promoted digestion and absorption of calcium and protein, while digestion and absorption of fat remained at a high level no matter what the condition was. Consequently, increasing the intake of fat would cause over nutrition. However, taking sustained-re- lease hydrochloric acid would reduce nutrient digestion and absorption.展开更多
Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy...Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.展开更多
We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role...We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.展开更多
High-performance liquid chromatography （HPLC） was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behav...High-performance liquid chromatography （HPLC） was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behavior. The effects of particle size and release medium pH on the release rate were also investigated. The indoor toxicity of emamectin benzoate-loaded polylactic acid microspheres on the diamondback moth larva （Plutella xylostella） was studied to explore drug sustained-release performance. In acidic and neutral media, the drug release behavior of the microspheres was in accord with the first-order kinetics equation. Increasing the spray dosage of emamectin benzoate-loaded polylactic acid microspheres initially resulted in an equivalent insecticidal efficacy with the conventional emamectin benzoate microemulsion. However, the drug persistence period was four-fold longer than that observed using the conventional formulation. The developed emamectin benzoate-loaded polylactic acid microspheres showed dramatic sustained-release performance. A treatment threshold of greater than 35 mg mL-1 was established for an efficient accumulated release concentration of emamectin benzoate-loaded microspheres.展开更多
The aroma sustained-release cotton fabric was prepared by finishing rose fragrance nanocapsules directly on cotton.The structure and properties of nanocapsules were demonstrated by transmission electron microscope(TEM...The aroma sustained-release cotton fabric was prepared by finishing rose fragrance nanocapsules directly on cotton.The structure and properties of nanocapsules were demonstrated by transmission electron microscope(TEM),dynamic light scattering(DLS),fourier transform infrared spectrometer(FTIR),X-ray diffraction (XRD),gas chromatography-mass spectrometry(GC-MS)and electronic nose.The results showed that the spherical nanocapsule dispersed evenly and the average diameter kept 51.4 nm.The existence of COO peak(1741 cm? 1)in the FTIR curve of the finished cotton fabric and the decrease of crystallinity demonstrated that rose fragrance nanocapsules have been incorporated into the cotton fabrics.The washing resistance of the cotton fabrics finished by 51.4 nm nanocapsules was much better than that by rose fragrance alone.Besides,the loss of fragrance from the cotton fabrics finished by 51.4 nm nanocapsules was obviously lower than that by 532 nm nanocapsules and rose fragrance.The smaller the nanocapsule size,the better the sustained release property.Electronic nose analysis also displayed that the aroma released from the cotton fabrics finished by nanocapsules after washing has no obvious variety in contrast to that without washing.The cotton fabrics finished by nanocapsules has the excellent sustained release property.展开更多
It is challenging for antibacterial polymer scaffolds to achieve the drug sustained-release through directly coating or blending.In this work,halloysite nanotubes(HNTs),a natural aluminosilicate nanotube,were utilized...It is challenging for antibacterial polymer scaffolds to achieve the drug sustained-release through directly coating or blending.In this work,halloysite nanotubes(HNTs),a natural aluminosilicate nanotube,were utilized as a nano container to load nano silver(Ag)into the lumen through vacuum negativepressure suction&injection and thermal decomposition of silver acetate.Then,the nano Ag loaded HNTs(HNTs@Ag)were introduced to poly-l-lactic acidide)(PLLA)scaffolds prepared by additive manufacturing for the sustained-release of Ag^+.Acting like a’shield’,the tube walls of HNTs not only retarded the erosion of external aqueous solution on internal nano Ag to generate Ag^+but also postponed the generated Ag^+to diffuse outward.The results indicated the PLLA-HNTs@Ag nanocomposite scaffolds achieved a sustained-release of Ag^+over 28 days without obvious initial burst release.Moreover,the scaffolds exhibited a long-lasting antibacterial property without compromising the cytocompatibility.Besides,the degradation properties,biomineralization ability and mechanical properties of the scaffolds were increased.This study suggests the potential application of inorganic nanotubes as drug carrier for the sustained-release of functional polymer nanocomposite scaffolds.展开更多
The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded ...The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.展开更多
Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate(HEMA)and Methyl methacrylate(MMA)cross-linked copolymer(P(HEMA-co-MMA))was prepared to examine the potential use for preventing poste...Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate(HEMA)and Methyl methacrylate(MMA)cross-linked copolymer(P(HEMA-co-MMA))was prepared to examine the potential use for preventing posterior capsule opacification(PCO).The preparations were prepared by polymerizing the mixture of HEMA,MMA,cross-linking agent(EGDMA),initiator(AIBN)and docetaxel.The influence factors and mechanism of drug release were studied in the experiments.FT-IR,X-RD and SEM methods were used to characterize the polymer(P(HEMA-co-MMA))and docetaxel-loaded sustained-release preparations.Biocompatibility of P(HEMA-co-MMA)and in-vitro effect of docetaxel-loaded sustained-release preparations were also evaluated.The results showed that docetaxel could release sustainedly from these preparations prepared by cross-linking polymerization.And the release rate could be accelerated by increasing the MMA ratio or EGDMA ratio of the polymer.Release mechanism of docetaxel fitted the Higuchi model well.The results of IR and X-RD showed that only a hydrogen bond was formed between docetaxel and P(HEMA-co-MMA).Docetaxel dispersed in P(HEMA-co-MMA)in amorphous form.The elution test showed that P(HEMA-co-MMA)had good biocompatibility and the in-vitro pharmacodynamics study proved that docetaxel could release stably from the preparations and inhibit HLECs’proliferation.The docetaxel-loaded sustained-release preparations proved to be a promising therapy for preventing PCO.These results also lay a theoretical and experimental foundation for the future.展开更多
The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. ...The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.展开更多
Allelochemicals sustained-release microspheres(ACs-SMs)exhibited great inhibition effect on algae,however,few studies have focused on ACs-SMs toxicity on invertebrate.In this study,the effects of single high-concentra...Allelochemicals sustained-release microspheres(ACs-SMs)exhibited great inhibition effect on algae,however,few studies have focused on ACs-SMs toxicity on invertebrate.In this study,the effects of single high-concentration ACs(15 mg/L,SH-ACs),repeated lowconcentration ACs(3×5 mg/L,RL-ACs)and ACs-SMs containing 15 mg/L ACs exposure on the ingestion,incorporation,and digestion of Daphniamagna Straus(DS)were investigated by stable isotope 15N labeling method.Meanwhile,the diversity and abundance of microflora in DS guts were determined by 16S rRNA genes and cloning methods.The results showed that SH-ACs exposure caused 50%and 33.3%death rates for newborn and adult DS,while RL-ACs exposure caused 10%death rate for newborn DS and no obvious effect on the activity of adult DS.And ACs-SMs exposure did not diminish the motility of both newborn and adult DS,indicating the lower acute toxicity of ACs-SMs.Furthermore,SH-ACs inhibited the ingestion(-6.45%),incorporation(-47.1%)and digestion(-53.8%)abilities of DS and reduced the microbial abundance(-27.7%)in DS guts.Compared with SH-ACs,RL-ACs showed relatively low impact on the ingestion(-3.23%),incorporation(-5.89%)and digestion(-23.9%)abilities of DS.Interestingly,ACs-SMs enhanced the ingestion(+9.68%),incorporation(+52.9%)and digestion(+51.3%)abilities of DS and increased the microbial abundance(+10.7%)in DS guts.Overall ACs and ACs-SMs reduced the diversity of microflora in DS guts.In conclusion,ACs-SMs can release ACs sustainably and prolong the sustained release time,which not only effectively reduce the toxicity of ACs,but also had positive effects on DS.展开更多
BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer i...BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer is still unelucidated.AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage Ⅱ and stage Ⅲ gastric cancer patients.METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release(SR) chemotherapy with 5-FU was used or not(NSR). The primary end-point was 5-year overall survival. Kaplan–Meier method with logrank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients.RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219(70.9%) were men, with an average age of 58.25 years. Furthermore, 56(18.1%) received neoadjuvant chemotherapy, and 191(61.8%) were in TNM stage Ⅲ. In addition, 158 patients received intraoperative sustainedrelease chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate(P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival.CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.展开更多
基金2023 Nantong Jianghai Talents Project2023 Nantong Social Livelihood Science and Technology Plan+4 种基金2021 Jurong Social Development Science&Technology Program(Grant No.ZA42109)2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research InstituteChina Postdoctoral Science Foundation(Grant No.2020M681532)Jiangsu Planned Projects for Postdoctoral Research Funds(Grant No.2020Z209)Natural Science Research Projects of Universities in Jiangsu Province(Grant No.20KJD350001)。
文摘Oseltamivir phosphate(OP),renowned as one of the most effective drugs for influenza treatment,encounters several challenges,including poor stability,difficulty in swallowing,and a bitter taste,thereby limiting its compliance,particularly among children.Consequently,this study aimed to devise a novel sustained-release suspension of OP employing an ion exchange resin as a carrier to address these challenges.The OP-drug resin complex(OP-DRC)was synthesized utilizing ion exchange technology,while OP-coated microcapsules(OP-CM)were fabricated via the emulsion-evaporation method.The optimization of the formulation process for the OP sustained-release suspension was achieved through a combination of single-factor experimentation and orthogonal experimental design.Furthermore,the drug release kinetics and pharmacokinetic properties of the sustained-release suspension were thoroughly evaluated both in vitro and in vivo.Scanning electron microscopy(SEM),X-ray diffraction(XRD),and attenuated total reflectance Fourier-transform infrared spectroscopy(ATR-FTIR)analyses confirmed the formation of drug-resin complexes via ionic bonding.The in vitro cumulative release rates were found to be 16%(1 h),53%(6 h),and 84%(24 h),respectively.Notably,the self-made sustained-release suspension exhibited an extended half-life(21.518 h),delayed time to peak concentration(T_(max))(6 h),and reduced maximum plasma concentration(C_(max))(0.397μg/mL)in comparison to commercial granules(half-life=8.466 h;T_(max)=2 h;C_(max)=0.631μg/mL).Additionally,the area under the curve(AUC)indicated that the bioavailability of the self-made OP suspension surpassed that of the commercial OP granules by 101%.These findings underscored the successful development of an oral OP sustained-release suspension characterized by stability,tastelessness,ease of swallowing,convenient administration,and sustained-release properties,thereby potentially enhancing drug compliance among children.
基金The 2022 Ministry of Education General Project for Humanities and Social Sciences Research(Grant No.22YJAZH147)the General Subject of Guangzhou Philosophy and Social Science Development“14th Five-Year Plan”in 2023(Grant No.2023GZYB68)+2 种基金China University Industry-Academia-Research Innovation Fund-Huatong Guokang Medical Research Special Project(Grant No.2023HT017)2024 Guangdong Province General Project for the Planning of Philosophy and Social Sciences(Grant No.GD24CGL29)the Innovation Team Project of Colleges and Universities in Guangdong Province(Grant No.2022WCXTD011).
文摘Different dosage forms can significantly impact pharmacokinetics in vivo,leading to varied effects and potential adverse reactions.This study aimed to evaluate the efficacy,safety,and cost-effectiveness of isosorbide mononitrate sustained-release capsules(IMSRC)combined with conventional treatments,compared to isosorbide mononitrate tablets(IMT)combined with conventional treatments,for managing angina pectoris in patients with coronary heart diseases.A network meta-analysis(NMA)was conducted to assess the efficacy and safety of IMSRC and IMT.Relevant literature was sourced from databases,including PubMed,Embase,Cochrane Library,ScienceDirect,Web of Science,CNKI,Wanfang,and VIP,covering publications up to July 2023.The cost-effectiveness analysis(CEA)was performed from the perspective of China’s healthcare system,utilizing inputs derived from the NMA.The analysis included 15 studies.The NMA results revealed no significant difference in efficacy and safety between IMSRC plus conventional treatments and IMT plus conventional treatments.However,both combinations were more effective than conventional treatments without isosorbide mononitrate.No differences in safety were observed among the three groups.The surface under the cumulative ranking(SUCRA)of the NMA indicated that IMT had a slight edge over IMSRC in the total effective rate of angina pectoris,whereas IMSRC showed higher probabilities for markedly effective rate and ECG effective rate compared to IMT.The incidence of adverse events was ranked as IMT>conventional preparation>IMSRC.The CEA results highlighted that the incremental cost-effectiveness ratios(ICERs)for the markedly effective and total effective rates of angina pectoris were-133.41 and-260.20,respectively.The ICERs for ECG effective rates were-83.34 and-234.24,respectively.In conclusion,while IMSRC combined with conventional treatments and IMT combined with conventional treatments were similar in efficacy and safety,IMSRC proved to be more economical.
基金Ministry of Science and Technology of China(Nos.2019YFC1805002 and 2018YFC1802300)National Natural Science Foundation of China(Nos.42177118 and 51779219)+1 种基金Basic Science Center Program for Multiphase Evolution in Hypergravity of the National Natural Science Foundation of China(No.51988101)Overseas Expertise Introduction Center for Discipline Innovation(No.B18047),China.
文摘Identification of chemical oxygen demand(COD)in municipal solid waste(MSW)landfill leachates is a challenging problem.This paper investigated the feasibility of using sodium persulfate(PS),a strong oxidant,as a permeable reactive barrier(PRB)filling material.Firstly,sustained-release persulfate balls were manufactured to adjust the release rate of persulfate,the oxidation agent.In addition,Fe(II)-loaded activated carbon(Fe-AC)was used to help with an even distribution of Fe(II)in the porous medium(PRB in this case).Then,the oxidation efficiency and kinetic rate of COD removal by the sustained-release balls were subjected to batch tests.A mass ratio of 1:1.4:0.24:0.7 for PS:cement:sand:water was the most efficient for COD removal(95%).The breakthrough curve for a 5 mm sustained-release ball revealed that the retardation factor was 1.27 and that the hydrodynamic dispersion coefficient was 15.6 cm^(2)/d.The corresponding half-life of COD oxidation was 0.43 d,which was comparable with the half-life of PS release from sustained-release balls(0.56 d).The sustained-release persulfate balls were shown to be an economical material with a simple recipe and production method when catalyzed by Fe-AC.Compared with cutting-edge methods,sustained-release balls used in PRBs offer significant advantages in terms of both effectiveness and economy for the preparation of sustained-release and catalytic materials.These results verified the feasibility of using sustained-release persulfate balls as a PRB material for COD removal.
基金This work was supported by the Key Programfor International Science and Technology Cooperation Projects of China(2020YFE0201700)State Drug Administration key laboratory project(2024HYZX04).
文摘The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping test.With their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release kinetics.The structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic structures.Furthermore,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic preparations.Moreover,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%ethanol.In conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.
文摘Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.
文摘Aim To improve the dissolution rate and bioavailability of silybin. Methods Sustained-release silybin microspheres were prepared by the spherical crystallization technique with soliddispersing and release-retarding polymers. A differential scanning calorimeter and an X-ray diffractometer were used to investigate the dispersion state of silybin in the microspheres. The shape, surface morphology, and internal structure of the microspheres were observed using a scanning electron microscope. Characterization of the microspheres, such as average diameter, size distribution and bulk density of the microspheres was investigated. Results The particle size of the microspheres was determined mainly by the agitation speed. The dissolution rate of silybin from microspheres was enhanced by increasing the amount of the dispersing agents, and sustained by the retarding agents. The release rate of microspheres was controlled by adjusting the combination ratio of the dispersing agents to the retarding agents. The resuits of X-ray diffraction and differential scanning calorimetry analysis indicated that silybin was highly dispersed in the microspheres in amorphous state. The release profiles and content did not change after a three-month accelerated stability test at 40 ℃ and 75% relative humidity. Conclusion Sustained-release silybin microspheres with a solid dispersion structure were prepared successfully in one step by a spherical crystallization technique combined with solid dispersion technique. The preparation process is simple, reproducible and inexpensive. The method is efficient for designing sustained-release microspheres with water-insoluble drugs.
基金The National Natural Science Foundation of China(Grant No.81460609)
文摘A qualitative and quantitative test method of fingerprint of Wuji gastric floating sustained-release tablets was established. High performance liquid chromatography （HPLC） was adopted, using Agilent ZORBAX SB-C18 column （250 mm×4.6 mm, 5 μm） as the chromatographic column, and acetonitrile-0.05 mol/L potassium dihydrogen phosphate solution as the mobile phase in a gradient elution with the flow rate of 1.0 mL/min. Sample solution （10 μL） was injected and was tested at the wavelength of 225 nm for 75 min at the column temperature of 30 ℃, Fingerprint similarity software （2004A version） was used to conduct data analysis. A total of 11 batches of Wuji gastric floating sustained-release tablets were tested and analyzed with HPLC fingerprint. Seventeen common peaks were found and the similarity of the 11 batches of agents was greater than 0.9, indicating that the production process of the agent is stable and feasible. The method is operable and could effectively control the quality of Wuji gastric floating sustained-release tablets.
文摘The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.
文摘This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.
基金Supported by National Natural Science Foundation of China(21576055)
文摘Rabbits with the body weight of （2.0 ± 0.5 ） kg were chosen, to study the effects of sustained-release calcium hydroxide and sustained-release hydro- chloric acid on nutrient digestion and absorption of rabbits. The results showed that sustained-release calcium hydroxide promoted digestion and absorption of nutri- ents, especially calcium and crude protein. The digestibility of calcium and crude protein was increased from 89.8% and 93.8% to 41.0% and 65.2%, respec- tively. Sustained-release hydrochloric acid was adverse to digestion and absorption of nutrients, especially calcium and crude protein. The digestibility of calcium and crude protein were decreased from 55.5% and 84.9% to 28.4% and 68.7%, respectively. The promotion effects of sustained-release hydrochloride on diges- tion lasted for 3 -4 d. Therefore, sustained-release calcium hydroxide promoted digestion and absorption of calcium and protein, while digestion and absorption of fat remained at a high level no matter what the condition was. Consequently, increasing the intake of fat would cause over nutrition. However, taking sustained-re- lease hydrochloric acid would reduce nutrient digestion and absorption.
基金supported by the Technology Fund of Zhangzhou City in China,No.Z2010086
文摘Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.
基金supported by the National Key Research and Development Program of China, No. 2016YFC1101603 (to DYZ)the National Natural Science Foundation of China, Nos. 31640045 (to YHW), 81901251 (to ML)the Natural Science Foundation of Beijing of China, No. 7204323 (to ML)
文摘We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.
基金supported by the National Key Research and Development Program of China (2016YFD0200502, 2017YFD0200301)
文摘High-performance liquid chromatography （HPLC） was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behavior. The effects of particle size and release medium pH on the release rate were also investigated. The indoor toxicity of emamectin benzoate-loaded polylactic acid microspheres on the diamondback moth larva （Plutella xylostella） was studied to explore drug sustained-release performance. In acidic and neutral media, the drug release behavior of the microspheres was in accord with the first-order kinetics equation. Increasing the spray dosage of emamectin benzoate-loaded polylactic acid microspheres initially resulted in an equivalent insecticidal efficacy with the conventional emamectin benzoate microemulsion. However, the drug persistence period was four-fold longer than that observed using the conventional formulation. The developed emamectin benzoate-loaded polylactic acid microspheres showed dramatic sustained-release performance. A treatment threshold of greater than 35 mg mL-1 was established for an efficient accumulated release concentration of emamectin benzoate-loaded microspheres.
基金Supported by the State Key Development Program for Basic Research of China(2009CB226104)the National Natural ScienceFoundation of China(20876097,21076125)+1 种基金Shanghai Chenguang Foundation(10CG60)Shanghai Excellent Talents(yyy10071)
文摘The aroma sustained-release cotton fabric was prepared by finishing rose fragrance nanocapsules directly on cotton.The structure and properties of nanocapsules were demonstrated by transmission electron microscope(TEM),dynamic light scattering(DLS),fourier transform infrared spectrometer(FTIR),X-ray diffraction (XRD),gas chromatography-mass spectrometry(GC-MS)and electronic nose.The results showed that the spherical nanocapsule dispersed evenly and the average diameter kept 51.4 nm.The existence of COO peak(1741 cm? 1)in the FTIR curve of the finished cotton fabric and the decrease of crystallinity demonstrated that rose fragrance nanocapsules have been incorporated into the cotton fabrics.The washing resistance of the cotton fabrics finished by 51.4 nm nanocapsules was much better than that by rose fragrance alone.Besides,the loss of fragrance from the cotton fabrics finished by 51.4 nm nanocapsules was obviously lower than that by 532 nm nanocapsules and rose fragrance.The smaller the nanocapsule size,the better the sustained release property.Electronic nose analysis also displayed that the aroma released from the cotton fabrics finished by nanocapsules after washing has no obvious variety in contrast to that without washing.The cotton fabrics finished by nanocapsules has the excellent sustained release property.
基金the National Natural Science Foundation of China(Nos.51935014,51905553,81871494,81871498,51705540)the Hunan Provincial Natural Science Foundation of China(Nos.2019JJ50774,2018JJ3671 and 2019JJ50588)+5 种基金the Jiang Xi Provincial Natural Science Foundation of China(No.20192ACB20005)the Guangdong Province Higher Vocational Colleges&Schools Pearl River Scholar Funded Scheme(2018)the Open Sharing Fund for the Large-scale Instruments and Equipments of Central South Universitythe Project of Hunan Provincial Science and Technology Plan(No.2017RS3008)the Hunan Provincial Innovation Foundation For Postgraduate(No.CX2018B093)the Fundamental Research Funds for the Central Universities of Central South University(Nos.2018zzts022 and 2019zzts725)。
文摘It is challenging for antibacterial polymer scaffolds to achieve the drug sustained-release through directly coating or blending.In this work,halloysite nanotubes(HNTs),a natural aluminosilicate nanotube,were utilized as a nano container to load nano silver(Ag)into the lumen through vacuum negativepressure suction&injection and thermal decomposition of silver acetate.Then,the nano Ag loaded HNTs(HNTs@Ag)were introduced to poly-l-lactic acidide)(PLLA)scaffolds prepared by additive manufacturing for the sustained-release of Ag^+.Acting like a’shield’,the tube walls of HNTs not only retarded the erosion of external aqueous solution on internal nano Ag to generate Ag^+but also postponed the generated Ag^+to diffuse outward.The results indicated the PLLA-HNTs@Ag nanocomposite scaffolds achieved a sustained-release of Ag^+over 28 days without obvious initial burst release.Moreover,the scaffolds exhibited a long-lasting antibacterial property without compromising the cytocompatibility.Besides,the degradation properties,biomineralization ability and mechanical properties of the scaffolds were increased.This study suggests the potential application of inorganic nanotubes as drug carrier for the sustained-release of functional polymer nanocomposite scaffolds.
文摘The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.
基金(Lab of Drug Metabolism and Pharmacokinetics,Sun Yat-sen University,Guangzhou,China)for the help and technical assistance.
文摘Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate(HEMA)and Methyl methacrylate(MMA)cross-linked copolymer(P(HEMA-co-MMA))was prepared to examine the potential use for preventing posterior capsule opacification(PCO).The preparations were prepared by polymerizing the mixture of HEMA,MMA,cross-linking agent(EGDMA),initiator(AIBN)and docetaxel.The influence factors and mechanism of drug release were studied in the experiments.FT-IR,X-RD and SEM methods were used to characterize the polymer(P(HEMA-co-MMA))and docetaxel-loaded sustained-release preparations.Biocompatibility of P(HEMA-co-MMA)and in-vitro effect of docetaxel-loaded sustained-release preparations were also evaluated.The results showed that docetaxel could release sustainedly from these preparations prepared by cross-linking polymerization.And the release rate could be accelerated by increasing the MMA ratio or EGDMA ratio of the polymer.Release mechanism of docetaxel fitted the Higuchi model well.The results of IR and X-RD showed that only a hydrogen bond was formed between docetaxel and P(HEMA-co-MMA).Docetaxel dispersed in P(HEMA-co-MMA)in amorphous form.The elution test showed that P(HEMA-co-MMA)had good biocompatibility and the in-vitro pharmacodynamics study proved that docetaxel could release stably from the preparations and inhibit HLECs’proliferation.The docetaxel-loaded sustained-release preparations proved to be a promising therapy for preventing PCO.These results also lay a theoretical and experimental foundation for the future.
基金supported by the Distinguished Professor Project of Liaoning Province(2015)
文摘The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.
基金supported by National Natural Science Foundation of China (Nos. 41977317, 42177051)Beijing Natural Science Foundation (No. 8182037)
文摘Allelochemicals sustained-release microspheres(ACs-SMs)exhibited great inhibition effect on algae,however,few studies have focused on ACs-SMs toxicity on invertebrate.In this study,the effects of single high-concentration ACs(15 mg/L,SH-ACs),repeated lowconcentration ACs(3×5 mg/L,RL-ACs)and ACs-SMs containing 15 mg/L ACs exposure on the ingestion,incorporation,and digestion of Daphniamagna Straus(DS)were investigated by stable isotope 15N labeling method.Meanwhile,the diversity and abundance of microflora in DS guts were determined by 16S rRNA genes and cloning methods.The results showed that SH-ACs exposure caused 50%and 33.3%death rates for newborn and adult DS,while RL-ACs exposure caused 10%death rate for newborn DS and no obvious effect on the activity of adult DS.And ACs-SMs exposure did not diminish the motility of both newborn and adult DS,indicating the lower acute toxicity of ACs-SMs.Furthermore,SH-ACs inhibited the ingestion(-6.45%),incorporation(-47.1%)and digestion(-53.8%)abilities of DS and reduced the microbial abundance(-27.7%)in DS guts.Compared with SH-ACs,RL-ACs showed relatively low impact on the ingestion(-3.23%),incorporation(-5.89%)and digestion(-23.9%)abilities of DS.Interestingly,ACs-SMs enhanced the ingestion(+9.68%),incorporation(+52.9%)and digestion(+51.3%)abilities of DS and increased the microbial abundance(+10.7%)in DS guts.Overall ACs and ACs-SMs reduced the diversity of microflora in DS guts.In conclusion,ACs-SMs can release ACs sustainably and prolong the sustained release time,which not only effectively reduce the toxicity of ACs,but also had positive effects on DS.
基金the CAMS Initiative for Innovative Medicine,No.2016-I2M-1-007。
文摘BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer is still unelucidated.AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage Ⅱ and stage Ⅲ gastric cancer patients.METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release(SR) chemotherapy with 5-FU was used or not(NSR). The primary end-point was 5-year overall survival. Kaplan–Meier method with logrank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients.RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219(70.9%) were men, with an average age of 58.25 years. Furthermore, 56(18.1%) received neoadjuvant chemotherapy, and 191(61.8%) were in TNM stage Ⅲ. In addition, 158 patients received intraoperative sustainedrelease chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate(P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival.CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.
