Designing of spherical chitosan nano-shells with micellar cores for solvation and safeguarded delivery of strongly lipophilic drugs

Abstract

Chitosan is a very effective biopolymer for drug delivery purposes due to its biocompatibility, positive charge and exceptionally pH sensitive degradability behavior in an aqueous medium. Nevertheless, its inability for dissolving lipophilic drug active material and the difficulties in controlling the size and shape of the synthesized particles in nanometer range are critical drawbacks in its effective use. In this study, a synthesis procedure which addresses both issues simultaneously is presented. The procedure is based on initial dissolution of lipophilic drug molecules within the hydrophobic cores of the micelles of a bio-compatible block-copolymer by ionic gelation and subsequent formation of a chitosan shell by polymerization around the micellar structures. Well-formed, hollow and perfectly spherical chitosan particles (nano-shells) in the 30–300 nm size range could be successfully manufactured. Characterization by STEM, TEM, AFM, FTIR and DLS, DLS-LDV techniques showed clearly that the drug was successfully incorporated into the chitosan structure. It was demonstrated that the particles enveloped the micelle(s) of a Pluronic copolymer (P-123) whose hydrophobic cores contained a strongly hydrophobic drug Probucol. The chitosan nano-shells are expected to act as an agent protecting the integrity of the drug-loaded micelles in the body fluid while providing a pH sensitive release medium. The drug uptake by the chitosan particles was very high. A very sharp increase in the amount of the drug released with a slight change in the acidity of the medium was an indication of the potential of the manufactured chitosan nano-shells as pH sensitive, target specific delivery vehicles for drug release.