Huperzine-A (Hup-A) is a reversible acetylcholinesterase inhibitor used for patients suffering from Alzheimer's disease. Hup-A has to be administered daily because of its short half-life time and narrow therapeutic range, making it less suitable for clinical use. In the present study, we studied its controlled drug delivery using biodegradable microspheres to avoid frequent dosing. Hup-A-loaded microspheres were prepared by an emulsion crosslinking method using a mixture of water and oil. Calcium chloride was used as a crosslinker. Primarily, we prepared sodium alginate (NaAlg) microspheres and 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 2h. 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 of the NaAlg/PVA-g-AAm (w/w) blend ratio, drug/polymer (w/w) ratio, crosslinker concentration and crosslinking period on the release of Hup-A was investigated. The prepared microspheres were characterized using Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy.