title: Controlled synthesis of N,N,N-trimethyl chitosan for modulated bioadhesion and nasal membrane permeability.
abstract: In an experiment to explore the bioadhesion, biocompatibility, and membrane permeation properties, the controlled synthesis of N,N,N-trimethyl chitosan (TMC) was carried out by two-step reductive methylation of chitosan (CHT). Methylation was confirmed by (1)H NMR (δ=3.1 ppm) and FTIR analysis (CH stretch at 1,485 cm(-1)). The TMC was further characterized by DSC, TGA, XRD, HR-TEM, SEM, and elemental analysis. Findings revealed improved solubility, enhanced viscosity, increased swelling index and higher molecular weight of TMC over CHT. Comparative evaluation validated increased bioadhesion potential, and improved ex vivo biocompatibility of TMC compared to CHT. Increased bioadhesion of TMC NPs over CHT NPs can be attributed to the strong electrostatic interactions between cationic amino groups with anionic sialic and sulfonic acid moieties contained in the mucin of the nasal mucus. Ex vivo biocompatibility studies suggested that the NP formulations of both biopolymers were biocompatible and could be applied safely on the nasal epithelium. Ex vivo permeation studies executed on excised cattle nasal mucosa illustrated improved permeability of TMC NPs over CHT NPs. In the author's opinion, two-step reductive methylation of CHT could be an attractive strategy to improve its solubility, bioadhesion, and permeation characteristics without affecting biocompatibility across the mucosal surfaces.
authors.affiliation: Industrial Pharmacy Laboratory, Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India. Electronic address: chandrakantpardeshi11@gmail.com.
authors.forename: Chandrakantsing V
authors.initials: CV
authors.lastname: Pardeshi
authors.affiliation: Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur, Maharashtra, India. Electronic address: vbelgamwar@gmail.com.
authors.forename: Veena S
authors.initials: VS
authors.lastname: Belgamwar
mesh_terms: D001704:Biopolymers / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000187:drug effects*; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008422:Materials Testing; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D012212:Rheology; D012995:Solubility; D013816:Thermodynamics
chemical_list: D001704:Biopolymers; C118071:N-trimethyl chitosan chloride; D048271:Chitosan
keywords: Chitosan; Methyl iodide (PubChem CID: 6328); Mucoadhesion; N,N,N-Trimethyl chitosan; N-Methyl-2-pyrrolidinone (PubChem CID: 13387); Nanoparticles; Nasal delivery; Polysaccharides; Reductive methylation; Sodium iodide (PubChem CID: 5238)