Studies of a novel nano sustained-released drug delivery system with a hydroxyapatite core and polysuccinimide coating structure

Abstract

In this study, a nano drug delivery system for sustained release (PSI–HAP) with spherical or near-spherical particles and a negative zeta potential was established. PSI–HAP was prepared using polysuccinimide (PSI) as the coating material and hydroxyapatite (HAP) as the drug adsorption core. By simply mixing PSI and HAP in solution, uniformly size non-agglomerated nanoparticles could be generated rapidly via a facile preparation process. Herein, HAP was prepared using the micro-emulsion method (MEM), liquid phase reaction (LPR), precipitation method (PM), or hydrothermal method (HM). The effects of the HAP preparation process on PSI–HAP were investigated. The optimal formulations and preparation processes of PSI–HAP were determined using single-factor experiments and the Box–Behnken design (BBD) response surface method with different model drugs. Additionally, the drug-loading and release features of PSI–HAP preparations were measured, and the distribution of SCE–PSI–HAP (Schisandra chinensis extract, SCE) in vivo was determined. The in vitro drug release test showed that PSI–HAPs were pH-sensitive, showing complete drug release around pH 7. Meanwhile, in vivo experiment demonstrated that in animals, the retention time was significantly longer in the SCE–PSI–HAP preparation group than in the saline group, irrespective of whether the formulation was administered orally or injected. The findings showed that the proposed drug delivery system is easy to prepare and sterilize, making large-scale production feasible, which could be used clinically for multi-modal drug delivery.