Cucurbit[7]-assisted sustained release of human calcitonin from thermosensitive block copolymer hydrogel

Conventional formulations of human calcitonin (hCT), a peptide drug, normally suffer from limited therapeutic efficacy with low stability and short half-life. We have found that the fibrillation of highly amyloidogenic hCT can be inhibited by cucurbit[7] (CB[7]), an amphiphilic small molecule. Meanwhile, a thermogelling copolymer was found to be a suitable candidate for sustained delivery of peptide/protein drugs. Herein, we report a long-term delivery formulation composed of hCT-CB[7] complex and biodegradable thermogel of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid −co-glycolic acid) (PLGA-PEG-PLGA). A 20 wt% PLGA-PEG-PLGA solution exhibited a temperature-sensitive sol-gel transition at 35 °C in phosphate buffer solution and slowly degraded over one month at neutral pH. Both the mass fraction of PLGA-PEG-PLGA copolymer and the complexation of hCT-CB[7] moderated the release process. hCT was sustainedly released over three weeks in the 20 wt% hydrogel with hCT-CB[7] complex at the ratio of 1:10 or 1:25. Further considering its low cytotoxicity, the delivery system is potential for the clinical application of hCT.

Biodegradable and biocompatible PLGA-PEG-PLGA thermogel system was developed and loaded with hCT-CB[7] complex for sustained release.152