Chitosan functionalized nanocochleates for enhanced oral absorption of cyclosporine A

Abstract

It remains a significant challenge to overcome the poor permeability of cyclosporine A and enhance its oral absorption. In this study, we have identified a positively charged chitosan that is able to induce coiling up of anionic lipids to form nanocochleates with an average size of 114.2 ± 0.8 nm, without the need for calcium ions. These functional chitosan-induced nanocochleates enhanced gastrointestinal absorption of cyclosporine A, up to a 3-fold increase in oral bioavailability. A fluorescence-labeling study confirmed that absorption mainly occurred in the duodenum and jejunum. Transport studies indicated that uptake of chitosan-induced nanocochleates by Caco-2 cells was by clathrin- and caveolae-mediated endocytosis, but not by macropinocytosis. Furthermore, three cellular tight junction proteins, ZO-1, F-actin and claudin-4, were significantly down-regulated, suggesting that chitobiose-induced nanocochleates are able to reconstruct and open tight junctions in intestinal epithelial cells to enhance drug absorption. In summary, these novel bifunctional chitosan-induced nanocochleates appear to have potential to facilitate oral delivery of cyclosporine A.

Synthesis and Evaluation of Herbal Chitosan from Ganoderma Lucidum Spore Powder for Biomedical Applications

“…Chitosan possesses good biocompatibility, biodegradability and low toxicity 10 and the materials absorptivity of heavy metal ions also makes it a valuable biopolymer 11 . For these reasons it has been used in numerous fields including food 12 , pharmaceutics and biomedical engineering 13 .…”

Recuperating Biopharmaceutical Aspects of Amphotericin B and Paromomycin Using a Chitosan Functionalized Nanocarrier via Oral Route for Enhanced Anti-leishmanial Activity

“…Chitosan is being accepted as a fascinating material for oral route delivery, which could be used as a permeation enhancer, mucoadhesion, and P-gp inhibition (Liu et al, 2017 ).…”

Water-in-Water Emulsion as a New Approach to Produce Mesalamine-Loaded Xylan-Based Microparticles

“…The preparation of microparticles based on hydrophilic polymers, such as polysaccharides derivatives, using techniques based on emulsion templates, majorly requires the use of organic solvents in order to form the hydrophilic and hydrophobic phases in which the internal hydrophilic phase contains the polymer [1][2][3]. In addition, together with the use of crosslinkers such as glutaraldehyde and terephthaloyl chloride, the microparticles produced by this way may present an important degree of toxicity [1,4].…”

“…The preparation of microparticles loaded with small active molecules through the water-in-water emulsion technique has been a pharmaceutical technology-based challenge. In this sense, in the present work, xylan microparticles loaded with mesalamine (5-ASA), which is a low molecular weight molecule, were prepared through a water-in-water emulsification process using different crosslinking approaches, designed through a 2 3 full factorial design with a central point.…”