Entecavir-loaded poly (lactic-co-glycolic acid) microspheres for long-term therapy of chronic hepatitis-B: Preparation and in vitro and in vivo evaluation

Abstract To avoid severe exacerbations in the load of hepatitis B virus (HBV) as a consequence of discontinuous use of anti-HBV drugs, entecavir (ETV), the first-line anti-HBV drug, was primally formulated as extended-release poly (lactic-co-glycolic acid) microspheres in the present study. Because ETV is slightly soluble in water and in some other organic solvents used for microsphere preparation, methods for solid-microencapsulation were employed to fabricate the ETV microspheres. The optimized microspheres were evaluated for their morphology, particle size, drug loading, in vitro drug release, and in vivo pharmacokinetics in rats. The optimized formulation was found to have a mean particle size of 86 µm and drug loading of 13%. Differential scanning calorimetry and powder X-ray diffraction indicated that ETV existed in crystal, amorphous, and molecular states in the microspheres. In vitro and in vivo release revealed that the dissolution of ETV dominated the release process. The morphology of the microspheres and changes in the morphology during in vitro release were assessed by scanning electron microscopy. The novel ETV-MS described in this study should have great potential for clinical use as an alternative treatment against HBV.