Cross-Linked Cationic Polymer Microparticles: Effect of N-Trimethyl Chitosan Chloride on the Release and Permeation of Ibuprofen

Abstract

Microparticles made by cross-linking hydrophilic polymers, such as chitosan, have been used to modify the release rate of a loaded drug. In this study a polymer with fixed positive charges, N-trimethyl chitosan chloride (TMC), was used in combination with chitosan to formulate microparticles to investigate its effects on drug release rate and transport across intestinal epithelial cells. The microparticles were prepared by cross-linking these cationic polymer(s) using sodium citrate as the ionic cross-linker. This process was done under homogenization and ultrasonication to control the size of the particles. The addition of TMC to the chitosan microparticles resulted in an increase in particle size of the microparticles and an increase in ibuprofen release rate as compared to the microparticles containing chitosan alone. Permeation of ibuprofen across Caco-2 cell monolayers, after administration of a suspension of the microparticles to the apical side, was not significantly different for the microparticles containing TMC as compared to those consisting of chitosan alone. It was concluded that release of TMC molecules from the microparticles was probably not sufficient to interact with the intestinal epithelial cells in order to change the permeation of the released drug.

Key Words:

• Chitosan
• N-trimethyl chitosan chloride
• Microparticles
• Drug release
• Drug transport