Controlled release of huperzine-A from biocompatible copolymer microspheres

[摘要] Huperzine-A (Hup-A) is a reversible acetylcholinesterase inhibitor used for patients suffering from Alzheimer’sdisease. Hup-A has to be administered daily because of its short half-life time and narrow therapeutic range, making it lesssuitable for clinical use. In the present study, we studied its controlled drug delivery using biodegradable microspheres toavoid frequent dosing. Hup-A-loaded microspheres were prepared by an emulsion crosslinking method using a mixture ofwater and oil. Calcium chloride was used as a crosslinker. Primarily, we prepared sodium alginate (NaAlg) microspheresand investigated the in vitro release. The in vitro release studies were carried out successively at three different pH (1.2, 6.8 and 7.4) values for 2 h. To increase the durability of the NaAlg microspheres, NaAlg was blended with acrylamide (AAm)-grafted poly(vinyl alcohol) (PVA). It was determined that the presence of the PVA-$g$-AAm increased the physical resistance of the microspheres and also increased the amount of Hup-A loading and release. Additionally, the effect ofthe NaAlg/PVA-$g$-AAm (w/w) blend ratio, drug/polymer (w/w) ratio, crosslinker concentration and crosslinking periodon the release of Hup-A was investigated. The prepared microspheres were characterized using Fourier transform infraredspectroscopy, differential scanning calorimetry and scanning electron microscopy.

[学科分类] 材料工程

[关键词] Huperzine-A;drug-delivery systems;controlled release;Alzheimer’s disease;graft copolymer.