Studies on the formulation optimization and controlled ionic gelation of chitosan nanoparticles using TPP-HP-β-CD inclusion complex

Abstract

Background and Aims: Ionic gelation strategy is the most common method used for the preparation of chitosan nanoparticles to obtain controlled drug delivery. Although it is a convenient and easy method, it is highly related with particle aggregation, high polidispersity index and insufficient physical/chemical stability. The aim of this study was the development of chitosan nanoparticles using tripolyphosphate-hydroxy propyl β-cyclodextrin or tripolyphosphate-sulfobutyl ether β-cyclodextrin inclusion complex as an alternative to TPP, and hence to increase physical stability, reduce polidispersity index and develop a stable nanocarrier for drug delivery purposes. Methods: The nanoparticles were prepared with the ionic gelation technique. The effects of chitosan percent, pH, and chitosan/tripolyphosphate ratio were investigated to find out the optimum nanoparticles in terms of particle size, polidispersity index and zeta potential. After determining the conditions for the tripolyphosphate-chitosan nanoparticles, the nanoparticles were prepared using tripolyphosphate-hydroxypropyl β-cyclodextrin or tripolyphosphate-sulfobutyl ether β-cyclodextrin to make a comparison with the nanoparticles which were prepared using tripolyphosphate. Results: The chitosan/tripolyphosphate-hydroxypropyl β-cyclodextrin nanoparticles were successfully formulated with 178 ± 84.1 nm particle size, 0.310±0.0134 PDI, 31.2±4.68 mV zeta potential. The interday changes in the measured characteristics were minimized for chitosan/tripolyphosphate-hydroxypropyl β-cyclodextrin nanoparticles as intended. Conclusion: CS/TPP-HP-β-CD nanoparticle formulation with particle size below 200 nm, high zeta potential and increased physical stability nanoparticles would offer a promising approach especially for hydrophobic drugs to improve their stability, solubility, encapsulation efficiency and in vivo bioavailability.

Keywords

• Chitosan nanoparticles,controlled ionic gelation,cyclodextrins

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