Betamethasone dipropionate intercalated layered double hydroxide and the composite with liposome for improved water dispersity

Abstract A hierarchical nanocomposite of betamethasone dipropionate (BDP), a nonionic and lipophilic glucocorticoid drug, intercalated layered double hydroxide (LDH) encapsulated in liposome was constructed by combining host-gest chemistry with a core-shell strategy, to develop a LDH-based drug delivery system with remarkable water dispersity and good sustained-release performance. BDP molecules were first incorporated into sodium cholate (Ch) micelles, and the negatively charged BDP-loaded micelles were then coassembled with positively charged LDH single-layer nanosheets, forming a BDP/Ch intercalated LDH (BDP-Ch-LDH) gest-host nanohybrid. The BDP-Ch-LDH was further coated with liposome (LS) consisting of lecithin and cholesterol, gaining a core-shell nanocomposite, denoted as (BDP-Ch-LDH)@LS. The BDP-Ch-LDH and (BDP-Ch-LDH)@LS were characterized using small angle X-ray scanning, Fourier-transform infrared, transmission electron microscopy, and elemental analyses. Their water dispersity and stability as well as in vitro drug release behavior were investigated. The particle size and sedimentation rate of freeze-dried (BDP-Ch-LDH)@LS redispersed in water (~ 190 nm and 0.035 mm/h, respectively) are obviously lower than those of BDP-Ch-LDH (~ 761 nm and 1.028 mm/h, respectively). The maximum percentage releases of the (BDP-Ch-LDH)@LS in pH 7.4 and 4.8 PBSs (~ 60% and 80%, respectively) are also lower than those of the BDP-Ch-LDH (both ~ 90%) under the studied conditions. These results demonstrated that the (BDP-Ch-LDH)@LS has remarkable water dispersity and stability as well as enhanced drug sustained-release performance in comparison with BDP-Ch-LDH. The liposome-coating modification is an effective strategy for improving the practical performance of LDH-based drug delivery system.