Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting trea...Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.展开更多
Transmucosal drug administration represents a potential strategy for enhancing treatment efficacy and reducing side effects by avoiding the first-pass effect into the systemic circulation and delivering therapeutics d...Transmucosal drug administration represents a potential strategy for enhancing treatment efficacy and reducing side effects by avoiding the first-pass effect into the systemic circulation and delivering therapeutics directly to the target disease site.However,many challenges still remain in its clinical application,including low drug availability and limited retention time in the mucosa.The burgeoning advancement of nanotechnologies offers great potential to overcome the above limitations,leveraging their distinct advantages of high drug-loading capacity and strong permeability.In this review,the latest developments of nanoparticles(NPs)in transmucosal drug delivery as well as their clinical applications are discussed.展开更多
An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were dis...An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were distributed evenly, and the particle size ranged from 20 to 260 nm（ average size ： 67.5 nm ）. Soybean lecithin played an important role in the emulsion system due to its abilities of acting as both absorption enhancer for insulin uptake through sublingual mucosa and oily phase for the emulsion system. The laser confocal scanning microscopic（LCSM） study showed that FITC-labelled insulin could penetrate the sublingual mucosa of rabbits, and the phase diagrams of the emulsion system suggested that soybean lecithin could take the place of oily phase to construct a stable emulsion system even if the traditional oil was absent. The applications of soybean lecithin as pharmaceutical biomaterial were extended for the further usage by present studies.展开更多
基金the financial support from the National Natural Science Foundation of China(Nos.82003678,82222066,82025032)Chinese Pharmacopoeia Commission(No.2021Y30)。
文摘Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.
基金supported by the National Natural Science Foundation of China(No.82100911)the Zhejiang Provincial Natural Science Foundation(No.LQ18H070004)to X.Y.+4 种基金the Zhejiang Provincial Natural Science Foundation(No.LY19H070002)to Y.X.S.the National Natural Science Foundation of China(No.32271380)to J.C.Y.,the National Natural Science Foundation of China(No.81970714)the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China under Grant No.LHDMZ23H070001Science and technology innovation leading talent project of Zhejiang ten thousand people plan(No.2021R52022)Zhejiang province health innovative talents project(No.2021-CXRC07-01)to X.H.W.
文摘Transmucosal drug administration represents a potential strategy for enhancing treatment efficacy and reducing side effects by avoiding the first-pass effect into the systemic circulation and delivering therapeutics directly to the target disease site.However,many challenges still remain in its clinical application,including low drug availability and limited retention time in the mucosa.The burgeoning advancement of nanotechnologies offers great potential to overcome the above limitations,leveraging their distinct advantages of high drug-loading capacity and strong permeability.In this review,the latest developments of nanoparticles(NPs)in transmucosal drug delivery as well as their clinical applications are discussed.
文摘An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were distributed evenly, and the particle size ranged from 20 to 260 nm（ average size ： 67.5 nm ）. Soybean lecithin played an important role in the emulsion system due to its abilities of acting as both absorption enhancer for insulin uptake through sublingual mucosa and oily phase for the emulsion system. The laser confocal scanning microscopic（LCSM） study showed that FITC-labelled insulin could penetrate the sublingual mucosa of rabbits, and the phase diagrams of the emulsion system suggested that soybean lecithin could take the place of oily phase to construct a stable emulsion system even if the traditional oil was absent. The applications of soybean lecithin as pharmaceutical biomaterial were extended for the further usage by present studies.
