Chitosan/calcium phosphate flower-like microparticles as carriers for drug delivery platform

Abstract

A special flower-like chitosan (CS)/calcium phosphate (CaP) microparticle was fabricated as a novel pH-sensitive carrier for sustained release drug system via a rapid one-pot approach. The CS-tripolyphosphate (TPP) nanocomplexes were firstly prepared through ionotropic gelation. Then, the CS nanocomplexes network acted as the template and inducer for adsorbing the mineralized CaP nanosheets and directing its assembly into the flower-like microparticles. The preparation condition optimized by Box-Behnken design-response surface methodology was achieved with 3.16 mg/ml of CS, 127.22 mg/ml of TPP, and 89.50 mM of CaCl2. The morphologies of the system were observed by scanning electron microscopy (SEM) and transmission electron microscope (TEM), and it showed that the flower-like microparticles with a diameter of 5–7 μm are composed of sheet-like petals with about 40 nm in thickness. And the TEM results showed that the petals consist by nanosheets with the thickness of 2–5 nm. The X-ray diffraction (XRD) results showed that the P/Ca ratio of CS/CaP microparticles is 1.29/1. The in vitro release studies demonstrated well sustained-release properties and pH-sensitive releasing characteristic of CS/CaP microparticles. The drug release mechanism was fitted by Korsmeyer-Peppas model at a pH of 5.8 and 7.4, respectively. The in vitro cell viability research demonstrated the microparticles have no obvious cytotoxicity at the dosages below 500 μg/ml. This work supplied a versatile platform as a novel drug delivery system with excellent pH-sensitive and sustained release performances.