Enhanced Intestinal Permeation of Doxorubicin Using Chitosan Nanoparticles

Abstract

Purpose: Due to limited oral bioavailability of doxorubicin (Dox) many efforts during the last decades focused on the development of novel delivery systems to overcome these limitations. In the present study, Dox encapsulated chitosan nanoparticles were prepared to evaluate the intestinal permeation of Dox via oral administration. Methods: Nanoparticles were fabricated based on ionic gelation method using tripolyphosphate. Some physicochemical properties, such as nanoparticle size and morphology, loading efficiency and in vitro drug release in 3 different pH values (5.0, 6.8 & 7.4) were evaluated. Intestinal permeations of free Dox and Dox loaded in nanoparticles were assessed using rat intestinal sac model. Results: The nanoparticles were spherical shape with average size of 150 10 nm. The entrapment and loading efficiency of Dox were up to 40% and 23%, respectively. According to the release profiles, up to 30% of loaded drug was released within 6hrs and the remaining amount of Dox was released more gradually, but this pattern was related to pH of the medium. The amount of drug released at acidic condition (pH 5.0) was greater than other pHs. The intestinal permeation of Dox increased nearly up to 90% by loading in chitosan nanoparticles. Conclusion: Using chitosan nanoparticles presents a potential safe drug delivery system for oral administration of Dox. In vivo studies and the determined pharmacokinetic and pharmacodynamic of Dox loaded chitosan nanoparticles after oral administration are planned for future studies.

Keywords

• Doxorubicin
• Chitosan nanoparticles
• Oral delivery
• Intestinal permeation
• Everted rat gut method