Anchalee Jintapattanakit

Physicochemical properties and biocompatibility of N-trimethyl chitosan : Effect of quaternization and dimethylation

The aim of this research was to investigate the effect of degrees of quaternization (DQ) and dimethylation (DD) on physicochemical properties and cytotoxicity of N-trimethyl chitosan (TMC). TMC was synthesized by reductive methylation of chitosan in the presence of a strong base at elevated temperature and polymer characteristics were investigated. The number of methylation process and duration of reaction were demonstrated to affect the DQ and DD. An increased number of reaction steps increased DQ and decreased DD, while an extended duration of reaction increased both DQ and DD. The molecular weight of TMC was in the range of 60-550kDa. From the Mark-Houwink equation, it was found that TMC in 2% acetic acid/0.2M sodium acetate behaved as a spherical structure, approximating a random coil. The highest solubility was found with TMC of an intermediate DQ (40%) regardless of DD and molecular weight. The effect of DD on the physicochemical properties and cytotoxicity was obviously observed when proportion of DD to DQ was higher than 1. TMC with relatively high DD showed reduction in both solubility and mucoadhesion and hence decreased cytotoxicity. However, the influence of DD was insignificant when DQ of TMC was higher than 40% at which physicochemical properties and cytotoxicity were mainly dependent upon DQ.

The role of mucoadhesion of trimethyl chitosan and PEGylated trimethyl chitosan nanocomplexes in insulin uptake

The aim of this work was to investigate the role of mucoadhesion in the insulin uptake of nanocomplexes (NC) based of trimethyl chitosan (TMC) and poly(ethylene glycol) (PEG)-graft-TMC copolymers. Self-assembled insulin NC were prepared by polyelectrolyte complexation. The effects of PEGylation and positive charge density on mucoadhesion were assessed using a mucin assay and mucus-secreting HT29-MTX-E12 (E12) monolayers. The behaviors of corresponding insulin NC after adhesion to E12 were also established. All PEGylated TMC copolymers showed significantly higher levels of adhesion to mucus than unmodified TMC. The copolymer composed of 298 PEG chains per TMC macromolecules exhibited the highest level of mucoadhesion, being 3.4 times higher than TMC. The higher mucoadhesive properties of PEGylated TMC copolymers resulted from the synergistic effects of interpenetration of PEG chains into the mucus and electrostatic interaction between positive charged TMC and anionic glycoproteins present in the mucus layer. Compared to TMC, insulin NC based on PEGylated TMC copolymers demonstrated no evidence of insulin uptake improvement due to complete release of insulin from NC after adhering to mucus. CLSM revealed the localization of TMC and its corresponding insulin NC at cell surface membranes of E12.

Nasal absorption and local tissue reaction of insulin nanocomplexes of trimethyl chitosan derivatives in rats

Objectives The objective of this work was to explore the potential and safety of trimethyl chitosan (TMC) and PEGylated TMC for improved absorption of insulin after nasal administration.

Effect of binary solid lipid matrix of wax and triglyceride on lipid crystallinity, drug-lipid interaction and drug release of ibuprofen-loaded solid lipid nanoparticles (SLN) for dermal delivery

HYPOTHESISnThe physicochemical properties of solid lipid nanoparticles (SLN) depend on lipid compositions. An addition of secondary solid complex triglycerides (Softisan 378; S378) into solid wax (cetyl palmitate; CP) is expected to influence the properties of obtained SLN compared to SLN prepared from sole CP.nnnEXPERIMENTSnIbuprofen-loaded SLN (IBSLN-TG) composed of different ratios of CP and S378 were prepared and evaluated in term of size, zeta potential (ZP), entrapment efficiency (E.E.), crystallinity, lipid-drug interaction and in vitro drug release.nnnFINDINGSnAfter production, all developed IBSLN-TG prepared from different ratios of CP and S378 had the particle size in the nanometer range (180-200nm) with the ZP values of higher than |-40mV| and possessed approximately 100% E.E. The release of IBSLN-TG demonstrated the biphasic pattern with a fast release followed by sustained release, which was fitted to Higuchis kinetics. The addition of S378 into CP-matrix led to a slight decrease in particle size and surface charge, and distortion of CP crystallization. The results from 1H-NMR indicated the formation of tiny liquid S378 nanocompartments within CP-matrix. The localization of ibuprofen in the S378 nanocompartments and the interaction between ibuprofen and S378 had an impact on the release profiles of IBSLN-TG depending on the ratios of CP and S378.