Self-assembled chitosan-insulin oral nanoparticles - A critical perspective review.

Chitosan is an abundant natural cationic polysaccharide with excellent biodegradability, bioadhesion, and biocompatibility. Chitosan is extensively researched for various particulate oral insulin drug delivery systems. Oral insulin is economically efficient and more convenient than injections, with greater patient compliance. Electrostatic ionic interaction between cationic chitosan and anionic polymer or insulin leads to the formation of spontaneously self-assembled nanoparticles. This simple technique attracted many researchers as it can be carried out quickly in mild conditions without harmful solvents, such as surfactants or chemical cross-linkers that might degrade the insulin structure. The formulated chitosan nanoparticles help to protect the core insulin from enzymatic degradation in the digestive system and improve paracellular intestinal uptake from the enterocytes due to mucoadhesion and reversible tight junction opening. Moreover, functionalized chitosan nanoparticles create newer avenues for targeted and prolonged delivery. This review focuses on modified chitosan-insulin nanoparticles and their implications on oral insulin delivery. Dependent variables and their optimal concentration ranges used in self-assembly techniques for chitosan-insulin nanoparticular synthesis are summarized. This review provides a comprehensive guide to fine-tune the essential factors to formulate stable insulin-chitosan nanoparticles using mild ionic interactions.

Evaluation of the Cytotoxicity of Levodopa and its Complex with Hydroxypropyl-ß-Cyclodextrin (HP-ß-CD) to an Astrocyte Cell Line.

A simple, reliable a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, (MTS) assay was conducted to evaluate the potential cytotoxic effects of levodopa, a "gold standard therapy" for Parkinsonism, and its complex with Hydroxypropyl-ß-Cyclodextrin (HP-ß-CD) on an astrocyte cell line. The cells were incubated in a range of concentrations from 4.69 to 300 µg/mL levodopa, HP-ß-CD or the complex for up to 72 hours. At every 24-hour interval, the optical density (OD), which reflects the number of viable cells, was recorded. In general, linear dose-dependent cytotoxicity profiles were observed for the cells subjected to levodopa or the complex, whereas a slightly triphasic response was observed for the cells exposed to HP-ß-CD. A significant difference (P < 0.05) in cytotoxicity was detected between the HP-ß-CD-treated group and the levodopa-treated group. In particular, we observed that the cells treated with the complex, even at the highest concentrations (> 200 µg/mL), exhibited improved tolerability in a time-dependent manner, which may indicate the potential ability of HP-ß-CD to mask the toxic effects of levodopa via complexation.

Cytotoxicity evaluation of vancomycin and its complex with beta-cyclodextrin on human glial cell line.

The possible cytotoxic effects of vancomycin and its complex with beta-cyclodextrin (ß-CD) on human glial cell line (CRL 8621) were studied accordingly by means of MTS assay. The cultured cells were incubated with various concentrations of vancomycin, ß-CD as well as ß-CD/vancomycin complex ranging from 4.69 to 300 ug/ml. A linear dose-dependency cytotoxicity followed by hermetic-like biphasic dose-dependence was observed after incubation period of 72 hours. In general, significant increase (p<0.001) of cell proliferation was observed at lower concentrations: <18.75 µg/ml for cells treated with ß-CD and their complex while < 9.38 µg/ml for cells treated with vancomycin. In contrary, regardless of the treatments given, significant (p<0.001) reduce in cell survival was found at higher concentrations >150 µg/ml. In particular, 50 % inhibitory in vitro was achieved at the concentrations of 115.95 µg/ml (for ß-CD), 116.48 µg/ml (for vancomycin) and 115.44 µg/ml (for ß-CD/vancomycin complex).