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transepithelial transport of nanoparticles in oral drug delivery:From the perspective of surface and holistic property modulation

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3876-3900页

作者： Yaxian Zheng Shiqin Luo Min Xu Qin He Jiang Xie Jiawei Wu Yuan Huang Department of Pharmacy the Third People’s Hospital of Chengduthe Affiliated Hospital of Southwest Jiaotong UniversityCollege of MedicineSouthwest Jiaotong UniversityChengdu 610031China Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Despite the promising prospects of nanoparticles in oral drug delivery,the process of oral administration involves a complex transportation pathway that includes cellular uptake,intracellular trafficking,and exocytosis by intestinal epithelial cells,which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic *** researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells,including surface properties such as ligand modification,surface charge,hydrophilicity/hydrophobicity,intestinal protein corona formation,as well as holistic properties like particle size,shape,and *** these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery ***,this review provides a comprehensive overview of the surface and holistic properties that influence the transepithelial transport of nanoparticles,elucidating the underlying principles governing their impact on transepithelial *** review also outlines the chosen of parameters to be considered for the subsequent design of oral drug delivery systems.

关键词： Oral delivery Nanoparticles Intestinal epithelial cells Surface property Holistic property transepithelial transport

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Changes in Antioxidant Activity of Alcalase-Hydrolyzed Soybean Hydrolysate under Simulated Gastrointestinal Digestion and transepithelial transport

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大豆科技 2019年第S1期 84-96页

作者： Zhang Qiaozhi Tong Xiaohong Qi Baokun Wang Zhongjiang Li Yang Sui Xiaonan Jiang Lianzhou 不详

Peptides from Alcalase-hydrolyzed soybean protein hydrolysate(SPH)may hold the potential as natural *** addition,the effect of human gastrointestinal(GI)tract on peptide bioavailability needs to be *** this study,the impact of simulated GI digestion and transepithelial transport on various antioxidant properties of SPH were *** displayed DPPH radical scavenging(IC50=4.22 mg/m L),ABTS·+radical scavenging(IC50=2.93 mg/m L),reducing power and metal ion-chelating activities(IC50=0.67 mg/m L).Furthermore,SPH significantly(Ptransepithelial transport,the permeates maintained partial antioxidant activity and the LC-MS/MS data further identified the absorbed soybean *** results suggest that SPH contains the antioxidant peptides that are potentially bioavailable and can be regarded as a promising source of functional food ingredients.

关键词： Soybean protein hydrolysate Antioxidant activity Simulated gastrointestinal digestion transepithelial transport Caco-2 cells

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Regulation of epithelial function, differentiation, and remodeling in the epididymis

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Asian Journal of Andrology 2016年第1期18卷 3-9页

作者： Sylvie Breton Ye Chun Ruan Yoo-Jin Park Bongki Kim Center for Systems Biology Program in Membrane Biology/Nephrology Division Massachusetts General Hospital Boston MA 02114 and Harvard Medical School Boston MA 02115 USA Epithelial Cell Biology Research Centre School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong Hong Kong China

The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation.

关键词： basal cells clear cells principal cells pseudostratified epithelia transepithelial transport

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Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles

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Acta Pharmaceutica Sinica B 2023年第9期13卷 3876-3891页

作者： Jiawei Wu Liyun Xing Yaxian Zheng Yinglan Yu Ruinan Wu Xi Liu Lian Li Yuan Huang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Protein corona(PC)has been identified to impede the transportation of intravenously injected nanoparticles(NPs)from blood circulation to their targeted ***,how intestinal PC(IPC)affects the delivery of orally administered NPs are still needed to be ***,we found that IPC exerted“positive effect”or“negative effect”depending on different pathological conditions in the gastrointestinal *** prepared polystyrene nanoparticles(PS)adsorbed with different IPC derived from the intestinal tract of healthy,diabetic,and colitis rats(H-IPC@PS,D-IPC@PS,C-IPC@PS).Proteomics analysis revealed that,compared with healthy IPC,the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the ***,both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking,which increased the transcytosis from the ***,disease-specific IPC endowed NPs with higher intestinal absorption.D-IPC@PS posed“positive effect”on intestinal absorption into blood circulation for diabetic ***,CIPC@PS had“negative effect”on colitis treatment because of unfavorable absorption in the intestine before arriving *** results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.

关键词： Oral nanoparticles Pathological intestine Disease-specific Intestinal protein corona Proteomics analysis Intracellular trafficking transepithelial transport Intestinal absorption

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An　Ultrastructural　Study　of　Phagocytosis　and　transport　of　Formalized　Campylobacter　jejuni　By　M　Cells　into　Mouse　Peyer's　Patches

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The Journal of Biomedical Research 1994年第1期18卷 41-44页

作者：王维亚郭仁强

Suspension of formalized Campylobacter jejunt (2×10 CFU/ml)was injected into a bothend-ligated intestinal loop of ileum which contained some Peyer's patches from non-immunized adult mice after laparotomy under *** 1-hour post inoculation, the specimen was taken out and prepared for TEM and SEM *** results showed that bacteria adhered specifically on the surface of M cells of Peyer's *** microvilli and microfolds of the M cells fused to capture the bacteria and to form a large endocytotic vesicle in the cytoplasm of the M cell,then transported inward,and, at *** into the central cavity between ***, we found some of them were phagocytosed by lymphocytes.

关键词： M cell Campylobacter jejunt transepithelial transport Peyer's patch

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