Development and evaluation of chitosan and chitosan derivative nanoparticles containing insulin for oral administration

Abstract

Chitosan and chitosan derivative-based nanoparticles loaded with insulin were prepared by self-assembly, via electrostatic interactions between the negatively charged drug and the positively charged polymers. In the investigated chitosan derivatives, the amine groups were substituted to different extents (33, 52 or 99%) by 2-hydroxypropyl-3-trimethyl ammonium groups, rendering the polymers permanently positively charged, irrespective of the pH. This is an important property for this type of advanced drug delivery system, since the pH value changes throughout the gastrointestinal tract and electrostatic interactions are of crucial importance for the stability of the nanoparticles. Permanent positive charges are also in favor of mucoadhesion. In contrast, the electric charges of chitosan molecules depend on the pH of the surrounding medium. Since the solubility of the chitosan derivatives increased due to the introduction of quaternary ammonium groups, sodium tripolyphosphate (TPP) was added to the systems to create supplementary cross-links and stabilize the nanoparticles. The presence of TPP influenced both the dissolution of the polymer matrix as well as the resulting release kinetics. The underlying drug release mechanisms were found to be more complex than simple diffusion under constant conditions, likely involving also ionic interactions and matrix dissolution. The most promising formulation was based on a chitosan derivative with 33% substitution degree and characterized by a Z-average of 142 ± 10 nm, a zeta potential of 29 ± 1 mV, an encapsulation efficacy of 52 ± 3% and, most importantly, the release of insulin was sustained for more than 210 min.

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

“…As we have previously reported, low values of effective diffusion coefficient can be associated with the presence of electrostatic interactions between a positively charged protein/peptide, and the negatively charged Alg core composing the Alg/Chit NPs [10]. Hecq et al have shown that for small proteins (insulin), Chit NPs leads to diffusion coefficients values that are several orders of magnitude lower than expected, as compared to macroscopic hydrogels filled with hydrophilic drugs [49]. In addition, the fact that not all of the CXCL12 molecules were released, combined with the lower than expected effective diffusion coefficient, strongly suggest the presence of electrostatic interactions between CXCL12 and Alg polymer chains.…”

Chitosan nanoparticles as a modified diclofenac drug release system

“…Chitosan nanoparticles have characteristics like pH sensitivity, biocompatibility, and low toxicity, making them a promising candidate for new controlled release drug systems development. An interesting chitosan nanoparticles feature is the possibility to carry hydrophilic drugs such as peptides and proteins due to their hydrophilic character (Piras et al 2015;Poth et al 2015;Hecq et al 2015). Another relevant characteristic is the positively charged chitosan nanoparticle surface, which promotes electrostatic interaction with biological membranes that are negatively charged and improvement in nanoparticle stability in the presence of biological cations (Agnihotri et al 2004;Laranjeira and Fávere 2009).…”

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

“…2,3) Based on the characteristic properties of a polymeric carrier, a number of solid dispersion systems possessing various functional properties such as sustained release, pH-dependent release, self-emulsifying properties, and site-specific release have been developed. [4][5][6][7] In particular, amphiphilic polymers have been found to be beneficial for the enhancement of not only solubility but also of the oral bioavailability of poorly water-soluble compounds because they form micellar structures that contain the compound. 6,8) Soluplus ® , a graft copolymer consisting of polyvinyl caprolactam, polyvinyl acetate, and polyethyleneglycol, has been applied to the design of solid-dispersion formulations with poorly water-soluble substances to improve their solubility and bioavailability.…”