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Title: Simultaneous Effect of Thiolation and Carboxylation of Chitosan Particles Towards Mucoadhesive Oral Insulin Delivery Applications: An In Vitro and In Vivo Evaluation
Authors: Rekha, MR
Sharma, CP
Issue Date: Jan-2015
Publisher: Journal of Biomedical Nanotechnology. 2015;11:165-76.
Abstract: Thiomalyl chitosan (TCS), a pH sensitive thiolated chitosan derivative, was developed and investigated towards oral protein delivery application. Particles of z-average 364 ± 5.6 nm with a negative zeta potential of 14.4 mV was obtained by tripolyphosphate cross linking of TCS. The release of insulin from TCS particles was significantly restricted at pH 1.2 minimizing up to about < 10% in 3 hours. The permeation enhancement ratio was found to 13 times higher than the FD4 alone and was 1.6 times higher than the unmodified chitosan particles. The protein protective properties of the matrix were established in presence of pepsin and pancreatic enzymes. Confocal microscopy studies proved the tight junction opening of Caco-2 cells by these thiolated chitosan particles and the in vivo studies on diabetic rats established its potential towards oral peptide delivery with pharmacological availability (PA) of 1.5%. The significance of this work is to establish that, the presence of multiple functional groups having similar property in the same matrix can improve its suitability as a promising candidate for oral peptide delivery with improved release characteristics, mucoadhesion as well as protecting the insulin activity and enhancing the permeability across the intestinal wall.
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