One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good b...One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good biocompatibility,and thus been widely used as drug carrier.Hydrogel has good 3-dimensional mesh structure which is convenience for drugs release and storage.In this study,Eths were introduced into silk fibroin(SF)/polyvinyl alcohol(PVA)composite hydrogel to construct a novel TDDS through a green process.The Ethsomes(Eths)-SF/PVA composite hydrogel TDDS showed good mechanical properties(stress:(0.236±0.032)MPa;strain:(65.74±2.45)%).Also,skin fibroblasts can grow and proliferate well on this TDDS,indicating that this material has a good cytocompatibility.Furthermore,with doxorubicin hydrochloride(Dox)as a model drug loaded in ethosomes,in vitro studies showed that this TDDS was able to transdermally release Dox efficiently.Our data suggested this novel system had a good potential for application in TDD,though further evaluative study still needed to carry out.展开更多
Transdermal drug delivery system(TDDS)facilitates the controlled release of active ingredients penetrating through the skin,avoiding the liver first pass effect.Electrospinning is a simple process to fabricate ultrafi...Transdermal drug delivery system(TDDS)facilitates the controlled release of active ingredients penetrating through the skin,avoiding the liver first pass effect.Electrospinning is a simple process to fabricate ultrafine fibers with a higher specific surface area,making them excellent candidates for drug delivery.In current work,a novel silk fibroin(SF)nanofiber loaded with cationic ethosomes(CEs)was prepared via green electrospinning.The data of Fourier transform infrared spectroscopy(FTIR)and laser scanning confocal microscopy(LSCM)confirmed the existence of CEs in the SF nanofibers.The morphology of the nanofibers was not significantly affected by the incorporation of CEs as shown by scanning electron microscopy(SEM)images.The CEs-loaded SF nanofibrous patch(CEs-SFnP)showed good cytocompatibility as proved by both cell counting Kit-8(CCK-8)assay and SEM.Using doxorubicin hydrochloride(Dox)as a model drug,the transdermal performance of CEs-SFnP was evaluated through Franz diffusion cell against mouse skin.The results indicated that CEs-SFnP can effectively deliver drug into the skin,with a much higher permeation rate than the normal nanofibers without CEs.The as-spun CEs-SFnP in this study could find promising applications in TDDS.展开更多
Ethosomes are permeation-enhancing carriers, which significantly promote drug delivery into skin. Thus,the introduction of ethosomes into electrospun nanofibers may result in good effect on transdermal drug delivery. ...Ethosomes are permeation-enhancing carriers, which significantly promote drug delivery into skin. Thus,the introduction of ethosomes into electrospun nanofibers may result in good effect on transdermal drug delivery. In this work,a novel ethosome-loaded silk fibroin( SF) /polyethylene oxide( PEO) composite nanofiber was fabricated based on a green electrospinning process. The ethosome-loaded SF /PEO nanofiber was round and smooth as shown by scanning electron microscopy( SEM),and the incorporation of ethosome didn't significantly affect the morphology of the electrospun SF /PEO nanofiber. The data of Fourier transform infrares(FTIR)spectra suggested the existence of ethosome on the SF /PEO nanofiber and the transmission electron microscopy(TEM) clearly showed the distribution of ethosome on the ethosome-loaded SF nanofibers. This ethosome-loaded SF nanofibrous mat may have a promising application in transdermal drug delivery systems.展开更多
Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abunda...Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abundant in skin tissues,transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of aPD-1.In this study,a novel mannosylated chitosan(MC)-modified ethosome(Eth-MC)was obtained through electrostatic adsorption.The Eth-MC loaded with plasmid containing the IL-12 gene(pIL-12@Eth-MC)stimulated DCs to express mature-related molecular markers such as CD86,CD80,and major histocompatibility complex-II in a targeted manner.The pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique,and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch(termed a transcutaneous immunization(TCI)patch).The TCI patch showed a good performance on transdermal drug release.Animal experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of tumour.Furthermore,combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 monotherapy.The combination therapy significantly promoted the expression of IL-12,interferon-γand tumour necrosis factor-α,the infiltration of CD4+and CD8+T cells into tumour tissues,and thus promoted the apoptosis of tumour cells.The present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor therapy.This study was approved by the Institutional Animal Care and Use Committee at Donghua University(approval No.DHUEC-NSFC-2020-11)on March 31,2020.展开更多
基金Natural Science Foundation of Shanghai,China(No.12ZR1400300)the Innovation Foundation of Donghua University,China(No.EG2015067)+1 种基金the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry,China“111 Project”Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good biocompatibility,and thus been widely used as drug carrier.Hydrogel has good 3-dimensional mesh structure which is convenience for drugs release and storage.In this study,Eths were introduced into silk fibroin(SF)/polyvinyl alcohol(PVA)composite hydrogel to construct a novel TDDS through a green process.The Ethsomes(Eths)-SF/PVA composite hydrogel TDDS showed good mechanical properties(stress:(0.236±0.032)MPa;strain:(65.74±2.45)%).Also,skin fibroblasts can grow and proliferate well on this TDDS,indicating that this material has a good cytocompatibility.Furthermore,with doxorubicin hydrochloride(Dox)as a model drug loaded in ethosomes,in vitro studies showed that this TDDS was able to transdermally release Dox efficiently.Our data suggested this novel system had a good potential for application in TDD,though further evaluative study still needed to carry out.
基金This work was supported by the Project of the Science&Technology Commission of Shanghai Municipality,China(Nos.18490740400,20DZ2254900).
文摘Transdermal drug delivery system(TDDS)facilitates the controlled release of active ingredients penetrating through the skin,avoiding the liver first pass effect.Electrospinning is a simple process to fabricate ultrafine fibers with a higher specific surface area,making them excellent candidates for drug delivery.In current work,a novel silk fibroin(SF)nanofiber loaded with cationic ethosomes(CEs)was prepared via green electrospinning.The data of Fourier transform infrared spectroscopy(FTIR)and laser scanning confocal microscopy(LSCM)confirmed the existence of CEs in the SF nanofibers.The morphology of the nanofibers was not significantly affected by the incorporation of CEs as shown by scanning electron microscopy(SEM)images.The CEs-loaded SF nanofibrous patch(CEs-SFnP)showed good cytocompatibility as proved by both cell counting Kit-8(CCK-8)assay and SEM.Using doxorubicin hydrochloride(Dox)as a model drug,the transdermal performance of CEs-SFnP was evaluated through Franz diffusion cell against mouse skin.The results indicated that CEs-SFnP can effectively deliver drug into the skin,with a much higher permeation rate than the normal nanofibers without CEs.The as-spun CEs-SFnP in this study could find promising applications in TDDS.
基金Natural Science Foundation of Shanghai,China(No.12ZR1400300)Fundamental Research Funds for the Central Universities of China+1 种基金"111 Project"Biomedical Textile Materials Science and Technology of China(No.B07024)Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials(No.LK1111)
文摘Ethosomes are permeation-enhancing carriers, which significantly promote drug delivery into skin. Thus,the introduction of ethosomes into electrospun nanofibers may result in good effect on transdermal drug delivery. In this work,a novel ethosome-loaded silk fibroin( SF) /polyethylene oxide( PEO) composite nanofiber was fabricated based on a green electrospinning process. The ethosome-loaded SF /PEO nanofiber was round and smooth as shown by scanning electron microscopy( SEM),and the incorporation of ethosome didn't significantly affect the morphology of the electrospun SF /PEO nanofiber. The data of Fourier transform infrares(FTIR)spectra suggested the existence of ethosome on the SF /PEO nanofiber and the transmission electron microscopy(TEM) clearly showed the distribution of ethosome on the ethosome-loaded SF nanofibers. This ethosome-loaded SF nanofibrous mat may have a promising application in transdermal drug delivery systems.
基金supported by the Science&Technology Commission of Shanghai Municipality of China,Nos.18490740400,20DZ2254900the National Key Research&Development Program of China,No.2018YFC1706200.
文摘Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abundant in skin tissues,transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of aPD-1.In this study,a novel mannosylated chitosan(MC)-modified ethosome(Eth-MC)was obtained through electrostatic adsorption.The Eth-MC loaded with plasmid containing the IL-12 gene(pIL-12@Eth-MC)stimulated DCs to express mature-related molecular markers such as CD86,CD80,and major histocompatibility complex-II in a targeted manner.The pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique,and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch(termed a transcutaneous immunization(TCI)patch).The TCI patch showed a good performance on transdermal drug release.Animal experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of tumour.Furthermore,combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 monotherapy.The combination therapy significantly promoted the expression of IL-12,interferon-γand tumour necrosis factor-α,the infiltration of CD4+and CD8+T cells into tumour tissues,and thus promoted the apoptosis of tumour cells.The present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor therapy.This study was approved by the Institutional Animal Care and Use Committee at Donghua University(approval No.DHUEC-NSFC-2020-11)on March 31,2020.
