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Effects of the multilayer structures on Exenatide release and bioactivity in microsphere/thermosensitive hydrogel system.
Colloids and Surfaces. B, Biointerfaces 2018 November 2
Traditional polypeptide-loaded PLGA microspheres (PM) using emulsion electrospray techniques often exhibit unsteady release and limited bioactivity. To solve these two problems, an Exenatide (EXT)-loaded multilayer system composed ofPM and thermosensitive hydrogel was prepared by the emulsion electrospray technique in this study. Hydrogel mixture were loaded in PLGA microspheres as Depot-hydrogel to prepare Gel/PM. The PM/Gel and Gel/PM/Gel systems were obtained by dispersion of PM and Gel/PM into hydrogel mixture, respectively. EXT in Gel/PM/Gel showed a constantly in vitro release for 30 days, which was significantly enhanced in comparison of those in the PM/Gel and the Gel/PM. PM/Gel and Gel/PM/Gel showed diminished burst release and no platform period compared with PM and Gel/PM. And these could be because the introduced Matrix-hydrogel outside, as a buffer layer, inhibited burst releases and exhibited a sustained manner. The inner Depot-hydrogelstructure slowed the PLGA degradation rate and drug release rate. As well, more than 15-day blood glucose levels in KKAy mice were greatly maintained at 7.50-9.50 mmol/L after a single subcutaneous injection of Gel/PM/Gel (4.95 μg/kg). Spatial stability and further bioactivity of released EXT were well protected by EXT-hydrogel complexes, and undesirable uptake of EXT and microspheres via phagocytes were also decreased by PEG shell. Thus, the long-acting microspheres/hydrogel multilayer system prepared by emulsion electrospray technique showed promising potentials for loading hydrophilic polypeptides and proteins.
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