The intramuscular administration of long-acting injectable microparticles elicits a local macrophage uptake resulting in decreased bioavailability. Herein, we developed a ginkgolide B (GB) loaded Solid/Oil/Water (S/O/W) solid lipid microparticles (SLMs) which were modified by hydroxyethyl starch (HES) or poly(ethylene glycol) (PEG) with different surface densities to investigate the influence of surface properties on the cellular uptake and systemic drug exposure. The spherical SLMs with a mean particle size of 10 µm were prepared by melt emulsification and post-insertion method, showing controlled release profile with less than 10 % of GB released in first 2 h. HES-SLMs resulted in lowest degree of RAW264.7 macrophage uptake in vitro and a higher systemic drug exposure in rats than PEG coating SLMs, indicting the capability of thick HES layer of SLMs in evading cellular uptake and sustained GB release. Overall, HES modified SLMs possess a great potential as intramuscular injected drug delivery system to improved bioavailability.
Keywords: Cellular uptake; Hydroxyethyl starch; Solid lipid microparticles; Sustained release.
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