Microencapsulated bufalin: From membrane preparation to microspheres tailoring, and sustained release

Abstract

Microspheres are commonly implemented in drug delivery system to enhance drug bioactivity and reduce the toxicity. Membrane emulsification is a promising technique to be applied in the preparation of microspheres for sustained release due to its easy control of the particle size. Membranes with different properties on dual sides have shown superior properties in the application of membrane emulsification. In this work, membranes with open channels and sharp pore size distribution were prepared by the novel combined solvent crystallization and polymer diffusion (CCD) technique. For the first time, the feasibility of CCD membranes with dual properties were verified for the application of membrane emulsification. Bufalin-poly(lactic-co-glycolic acid) (PLGA) microspheres were successfully prepared and the size distribution could be tuned via adopting CCD membranes with different pore sizes. The effects of membrane wettability and pore size on microspheres production were investigated for the membranes prepared by four different cooling conditions. The morphologies of microspheres were obtained by scanning electron microscope and the size distribution was analyzed by ImageJ. The in vitro release of bufalin-PLGA microspheres in various sizes exhibited distinctively, indicating the capability of controlling the release rate of the drug system via changing membrane with different properties. In this study, the most uniformly distributed bufalin-PLGA microspheres with an average size of 0.47 µm were achieved through membrane emulsification using the optimal CCD membranes. The as-prepared bufalin-PLGA microspheres exhibited an IC50 of 231.7 µg/mL, achieving reduced toxicity than free bufalin. This study provides a novel approach on tailoring microspheres via the manipulation of membrane properties, facilitating the design and production of drug delivery system with desired properties for a wide range of purposes.