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

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We 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 intestine. Consequently, 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 epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These 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.

Bioavailability in vivo and in vitro transepithelial transport across Caco-2 cell monolayer of pueraria flavonoids bio-adhesive and floating pellets / 药学学报

To study the bioavailability of pueraria flavonoids bio-adhesive and floating pellets, the absorption of puerarin was studied using Caco-2 cell monolayer by liquid chromatography (HPLC) method, comparing the Papp of pueraria flavonoids bio-adhesive and floating pellets with different bio-adhesive materials. Drugs were administered at a dose of 100 mg·kg-1 via ig. The plasma concentration of puerarin was determined by HPLC, the pharmacokinetics were calculated with the WinNonlin 6.0 software. The results showed that the Papp of bio-adhesive and floating pellets with hydroxypropyl methylcellulose (HPMC)-cabomer was largest, which had a significant difference (P0-t of pueraria flavonoids bio-adhesive and floating pellets was 1.79 times of pueraria flavonoids, the Cmax of pueraria flavonoids bio-adhesive and floating pellets and pueraria flavonoids had a significant difference (P<0.05). What's more the MRT had prolonged. In conclusion, pueraria flavonoids bio-adhesive and floating pellets with HPMC-cabomer could significantly facilitate the transport of puerarin on Caco-2 cellular monolayers. The bioavailability of pueraria flavonoids bio-adhesive and floating pellets with HPMC-cabomer was increased more than pueraria flavonoids with a sustained release effect.

Regulation of epithelial function, differentiation, and remodeling in the epididymis / 亚洲男科学杂志(英文版)

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.