Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via c...Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Use of traditional physical and chemical enhancers to improve the transdermal permeation rate by increasing drug solubility, diffusion coefficient, and reservoir effect is not feasible owing to the toxic side effects of the overuse of chemical penetration enhancers. Nanoformulations generally vary in size and range from 10 nm to 100 nm. The smaller particle size leads to increased drug permeability, stability, retention, and targeting, making nano-formulations suitable for transdermal drug delivery. The different applications of nano-formulations(vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed.展开更多
In recent years,the continuous occurrence of multi-drug resistance in the clinic has made people pay more attention to the transporter.Changes in the expression and activity of transporters can cause corresponding cha...In recent years,the continuous occurrence of multi-drug resistance in the clinic has made people pay more attention to the transporter.Changes in the expression and activity of transporters can cause corresponding changes in drug pharmacokinetics and pharmacodynamics.The drug-drug interactions(DDI)caused by transporters can seriously affect drug effectiveness and toxicity.In the development of pharmaceutical preparations,people have increasingly concerned about the effects and regulation of transporters in drug effects.To improve the targeting and physicochemical properties of drugs,the development of targeted agents is very rapid.Among them,novel nano-formulations are the best.With the continuous innovation and development of nano-formulation,its application has become more and more extensive.Nano-formulation has exerted certain advantages in the drug development based on transporters,and is also involved in the combination of targeted transporters.This review focuses on the application of novel nano-agents targeting transporters and the introduction of drug-transporter-based nano-formulations.展开更多
Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high c...Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.展开更多
Current drugs against multiple human malignancies are limited,and developing new treatment strategies is improbable within a short time.So,considering the current situation,phytochemicals could be a viable option for ...Current drugs against multiple human malignancies are limited,and developing new treatment strategies is improbable within a short time.So,considering the current situation,phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies.Therefore,we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually.We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search,and these compounds have chemotherapeutic activities against around 15 different human malignancies.In vitro and preclinical models support that the chemotherapeutic properties of phytochemicals derived from Eclipta prostrata are believed to be regulated by many pathways,including targeting signaling pathways,for example,phosphoinositide 3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR),tumor necrosis factor-alpha(TNF-α),nuclear Factor-kappa B(NF-κB),mitogen-activated protein kinase(MAPK);regulated cell death such as Fas cell surface death receptor(FAS),Bid,apoptosis-inducing factor(AIF),Bcl2,Bax,Bak,Bad,caspase,and Poly(ADPribose)Polymerase(PARP);metastasis and angiogenesis such as matrix metalloproteinases(MMPs)(2&9),wingless/integrated(Wnt)/beta-catenin,angiogenesis(E-cCadherin&N-cadherin,vimentin),cell proliferation(cyclins-A,B1,D1,E1,and cyclindependent kinases(CDKs)1,2,4),inflammatory molecules(programmed death-ligand 1(PD-L1),TNF-α,NF-κB,Interleukin-1(IL-1),Interleukin-6(IL-6),Interleukin-8(IL-8),Interleukin-1 beta(IL-1β)),regulating tumor suppressor genes(p21,p27,p38,p51,p53),microRNA(miRNA)regulation,and some nonspecific pathways like DNA fragmentation damage and repair,autophagy(light chain 3-II(LC3-II)and mTOR),and many other pathways.Some selective phytochemicals exert synergistic activities with standard chemotherapeutic drugs and reverse drug resistance through several mechanisms.Nano-based phytochemicals target numerous cancer cells,resulting in drug accumulation and improved drug efficacy,making phytochemicals more potent chemotherapeutic agents in cancer treatment.Additionally,an in-silico pharmacokinetics study reveals that phytoestrogen possesses suitable pharmacokinetic characteristics with minor toxicity in the human body.So,direct consumption of different parts of Eclipta prostrata or specific phytochemicals from this plant can be a potential candidate drug against human malignancies.展开更多
Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability a...Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.展开更多
Curcumin, a polyphenol (diferuloylmethane), is a derivative obtained from the Curcuma longa. It has many beneficial functions, including pain-killing, activity against reactive oxygen species, preventing inflammation ...Curcumin, a polyphenol (diferuloylmethane), is a derivative obtained from the Curcuma longa. It has many beneficial functions, including pain-killing, activity against reactive oxygen species, preventing inflammation and antibacterial activities, for which it has been used for centuries in Ayurvedic medication. The mechanisms showing curcumin activity involve a grouping of signaling pathways in the cell at multiple stages. Recently, the anticancer effects of curcumin were studied on different pathways, including the gene expression for cancer, its spread, the regulation of cell cycle, programmed cell death, and tumor expression. All these studies suggest enormous potential of curcumin in cancer therapy. It has many more potential benefits against cardiovascular diseases, reactive oxygen species, bacteria and fungi. The present review provides a brief description of the studies conducted and the information supportive to pharmaceutical activities of curcumin. It also considers anticancer applications and clinical benefits of nano-formulations of curcumin.展开更多
Vitamin supplementation during chemotherapy has often been associated with lower recurrence and mortality rates in cancer patients.We had previously demonstrated that the multivitamin(C,D3,and B12)-cisplatin nanoparti...Vitamin supplementation during chemotherapy has often been associated with lower recurrence and mortality rates in cancer patients.We had previously demonstrated that the multivitamin(C,D3,and B12)-cisplatin nanoparticle complex-NanoCisVital(NCV)-could alleviate chemotherapy-induced cancer fatigue.Chitosan is frequently used in functional nanomaterials to encapsulate drugs,because it is biodegradable,biocompatible,and non-toxic.The chitosan-based NCVs were prepared,and their physicochemical properties,size,and stability were evaluated before assessing their effect on cancer cell lines.The multivitamin mixture is packed in the core,and cisplatin is loaded at the periphery of the nanoparticle.This encapsulation facilitates the slow and sequential release of peripheral cisplatin and the core multivitamin combination.By increasing the amounts of vitamin and drug-encapsulated nanoparticles in breast and cervical cancer cell lines,the viable cell percentage was calculated.DDX3X promotes cancer cell proliferation,invasion,and metastasis,while Ki-67 promotes active cell proliferation in all cell types.DDX3X is elevated in several cancer types,and breast cancer cells express it abnormally.The Ki-67 protein is a biomarker of cell proliferation that is present throughout all active stages of the cell cycle but undetectable in the resting state.The expression of the DDX3X and Ki-67 genes is altered in NCV-treated cells.This study uses DDX3X and Ki-67 gene expression as a comparative measuring tool for the anti-cancer and cell proliferation effects of cisplatin and vitamins,respectively.展开更多
基金supported by the Postdoctoral Innovation Talents Support Program(No.BX20180207)the National Nature Science Foundation of China(No.81502722)
文摘Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Use of traditional physical and chemical enhancers to improve the transdermal permeation rate by increasing drug solubility, diffusion coefficient, and reservoir effect is not feasible owing to the toxic side effects of the overuse of chemical penetration enhancers. Nanoformulations generally vary in size and range from 10 nm to 100 nm. The smaller particle size leads to increased drug permeability, stability, retention, and targeting, making nano-formulations suitable for transdermal drug delivery. The different applications of nano-formulations(vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed.
基金This work was supported by grants from National Natural Science Foundation of China(81773805 and 81973390)the National Key Research and Development Program of China(2017YFC0908600).
文摘In recent years,the continuous occurrence of multi-drug resistance in the clinic has made people pay more attention to the transporter.Changes in the expression and activity of transporters can cause corresponding changes in drug pharmacokinetics and pharmacodynamics.The drug-drug interactions(DDI)caused by transporters can seriously affect drug effectiveness and toxicity.In the development of pharmaceutical preparations,people have increasingly concerned about the effects and regulation of transporters in drug effects.To improve the targeting and physicochemical properties of drugs,the development of targeted agents is very rapid.Among them,novel nano-formulations are the best.With the continuous innovation and development of nano-formulation,its application has become more and more extensive.Nano-formulation has exerted certain advantages in the drug development based on transporters,and is also involved in the combination of targeted transporters.This review focuses on the application of novel nano-agents targeting transporters and the introduction of drug-transporter-based nano-formulations.
基金This work is supported by National Key Research and Development Program of China(No.2022YFC3501905)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)+2 种基金National Natural Science Foundation of China(NSFC,No.82104076)Science and Technology Commission of Shanghai Municipal(STCSM,No.22S21902400,China)Medicine-Engineering joint foundation of Shanghai Jiao Tong University(No.YG2022QN025 and YG2022QN050,China).
文摘Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.
文摘Current drugs against multiple human malignancies are limited,and developing new treatment strategies is improbable within a short time.So,considering the current situation,phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies.Therefore,we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually.We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search,and these compounds have chemotherapeutic activities against around 15 different human malignancies.In vitro and preclinical models support that the chemotherapeutic properties of phytochemicals derived from Eclipta prostrata are believed to be regulated by many pathways,including targeting signaling pathways,for example,phosphoinositide 3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR),tumor necrosis factor-alpha(TNF-α),nuclear Factor-kappa B(NF-κB),mitogen-activated protein kinase(MAPK);regulated cell death such as Fas cell surface death receptor(FAS),Bid,apoptosis-inducing factor(AIF),Bcl2,Bax,Bak,Bad,caspase,and Poly(ADPribose)Polymerase(PARP);metastasis and angiogenesis such as matrix metalloproteinases(MMPs)(2&9),wingless/integrated(Wnt)/beta-catenin,angiogenesis(E-cCadherin&N-cadherin,vimentin),cell proliferation(cyclins-A,B1,D1,E1,and cyclindependent kinases(CDKs)1,2,4),inflammatory molecules(programmed death-ligand 1(PD-L1),TNF-α,NF-κB,Interleukin-1(IL-1),Interleukin-6(IL-6),Interleukin-8(IL-8),Interleukin-1 beta(IL-1β)),regulating tumor suppressor genes(p21,p27,p38,p51,p53),microRNA(miRNA)regulation,and some nonspecific pathways like DNA fragmentation damage and repair,autophagy(light chain 3-II(LC3-II)and mTOR),and many other pathways.Some selective phytochemicals exert synergistic activities with standard chemotherapeutic drugs and reverse drug resistance through several mechanisms.Nano-based phytochemicals target numerous cancer cells,resulting in drug accumulation and improved drug efficacy,making phytochemicals more potent chemotherapeutic agents in cancer treatment.Additionally,an in-silico pharmacokinetics study reveals that phytoestrogen possesses suitable pharmacokinetic characteristics with minor toxicity in the human body.So,direct consumption of different parts of Eclipta prostrata or specific phytochemicals from this plant can be a potential candidate drug against human malignancies.
基金supported by the National Natural Science Foundation of China(NSFC,81971734,32071323,32271410),the Program for Innovative Research Team in Science and Technology in Fujian Province.
文摘Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.
文摘Curcumin, a polyphenol (diferuloylmethane), is a derivative obtained from the Curcuma longa. It has many beneficial functions, including pain-killing, activity against reactive oxygen species, preventing inflammation and antibacterial activities, for which it has been used for centuries in Ayurvedic medication. The mechanisms showing curcumin activity involve a grouping of signaling pathways in the cell at multiple stages. Recently, the anticancer effects of curcumin were studied on different pathways, including the gene expression for cancer, its spread, the regulation of cell cycle, programmed cell death, and tumor expression. All these studies suggest enormous potential of curcumin in cancer therapy. It has many more potential benefits against cardiovascular diseases, reactive oxygen species, bacteria and fungi. The present review provides a brief description of the studies conducted and the information supportive to pharmaceutical activities of curcumin. It also considers anticancer applications and clinical benefits of nano-formulations of curcumin.
基金supported by DST-SERB,India under grant No.EMR/2017/001294.
文摘Vitamin supplementation during chemotherapy has often been associated with lower recurrence and mortality rates in cancer patients.We had previously demonstrated that the multivitamin(C,D3,and B12)-cisplatin nanoparticle complex-NanoCisVital(NCV)-could alleviate chemotherapy-induced cancer fatigue.Chitosan is frequently used in functional nanomaterials to encapsulate drugs,because it is biodegradable,biocompatible,and non-toxic.The chitosan-based NCVs were prepared,and their physicochemical properties,size,and stability were evaluated before assessing their effect on cancer cell lines.The multivitamin mixture is packed in the core,and cisplatin is loaded at the periphery of the nanoparticle.This encapsulation facilitates the slow and sequential release of peripheral cisplatin and the core multivitamin combination.By increasing the amounts of vitamin and drug-encapsulated nanoparticles in breast and cervical cancer cell lines,the viable cell percentage was calculated.DDX3X promotes cancer cell proliferation,invasion,and metastasis,while Ki-67 promotes active cell proliferation in all cell types.DDX3X is elevated in several cancer types,and breast cancer cells express it abnormally.The Ki-67 protein is a biomarker of cell proliferation that is present throughout all active stages of the cell cycle but undetectable in the resting state.The expression of the DDX3X and Ki-67 genes is altered in NCV-treated cells.This study uses DDX3X and Ki-67 gene expression as a comparative measuring tool for the anti-cancer and cell proliferation effects of cisplatin and vitamins,respectively.
