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Chinese Journal of Polymer Science 1995年第4期13卷 315-321页

作者： Raphael M.Ottenbrite Sam Milstein Chemistry Department Virginia Commonwealth UniversityRichmond VA 23284-2006 USAEmisphere Technologies Inc. 15 Skyline Drive Hawthorne NY 10595 USA

An oral drug delivery system using proteinoid microspheres is discussed with respect to itsunique dependence on pH. It has been found that certain drugs such as insulin and heparin canbe encapsulated in proteinoid spheres at stomach pH's (1--3). These spheres also dissemble atintestinal pH's (6--7) releasing the drug for absorption. Using this technique low molecularweight heparin and human growth hormone have been orally delivered successfully to severalanimal species. Future work has been proposed to study the interaction and binding of thespecific drugs with synthesized oligopeptides.

关键词： oral drug delivery system Proteinoid microspheres Oligopeptides

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Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides

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Nano Research 2023年第7期16卷 9768-9780页

作者： Mengting Lin Linjie Wu Yiying Lu Xiaoyan Bao Haiqing Zhong Qi Dai Qiyao Yang Yiyi Xia Xin Tan Yaxin Qin Ruolin Jiang Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Pharmacy Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China The Second Affiliated Hospital College of MedicineZhejiang UniversityHangzhou 310058China

orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and ***,the development of oral protein formulations has stalled due to the low bioavailability of macromolecules that encounter the aggressive gastrointestinal environment and harsh mucus villi ***,we propose an ideal reverse micelle/self-emulsifying drug delivery system(RM/SEDDS)nanoplatform that is capable of improving the oral bioavailability of hydrophilic peptides by preventing enzymatic degradation and enhancing mucosal *** the passage through the mucus,the self-emulsifying drug delivery system with optimal surface properties effectively penetrates the viscoelastic mucosal barrier,followed by the exposure of the inner reverse micelle amphipathic vectors,which autonomously form continua with the lipidic cell membrane and facilitate the internalization of *** membrane-fusion mechanism inaugurates a new way for hydrophilic peptide delivery in the free form,circumventing the traditional impediments of the cellular internalization of nanocarriers and subsequent poor release of *** more importantly,reverse micelles are not spatially specific to the laden drugs,which enables their delivery for a myriad of peptide clinical *** conclusion,as an exquisitely designed nanoplatform,RM/SEDDS overcomes multiple physiological barriers and opens a new path for drug cellular entry,providing new prospects for the development of oral drug delivery systems.

关键词： oral drug delivery system reverse micelle self-emulsifying drug delivery system membrane fusion hydrophilic peptide

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Milk-derived exosomes exhibit versatile effects for improved oral drug delivery

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Acta Pharmaceutica Sinica B 2022年第4期12卷 2029-2042页

作者： Lei Wu Lingling Wang Xi Liu Yuli Bai Ruinan Wu Xiang Li Yutong Mao Ling Zhang Yongxiang Zheng Tao Gong Zhirong Zhang Yuan Huang Key Laboratory of drug Targeting and drug delivery system Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Sichuan University College of Polymer Science and EngineeringChengdu 610041China Sichuan University West China School of Pharmacy Chengdu 610041China

As endogenous courier vesicles,exosomes play crucial roles in macromolecule transmission and intercellular ***,exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few ***,few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral ***,the mechanisms underlying their biomimetic properties as oral delivery vehicles remain ***,insulin-loaded milk-derived exosomes(EXO@INS)were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic ***,EXO@INS(50 and 30 IU/kg)elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected *** mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake,pH adaptation during gastrointestinal transit,nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus *** study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.

关键词： Milk-derived exosomes oral drug delivery system Apical-to-basolateral transport pH Adaptation Biomimetic vehicles Insulin Transcytosis Signal regulation

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