Injectable coacervate hydrogel for delivery of anticancer drug-loaded nanoparticles in vivo.

In this study, Bortezomib (BTZ, a cytotoxic water-insoluble anticancer drug) was encapsulated in micellar nanoparticles having a catechol-functionalized polycarbonate core through a pH-sensitive covalent bond between phenylboronic acid in BTZ and catechol, and these drug-loaded micelles were incorporated into hydrogels to form micelle/hydrogel composite. A series of injectable, biodegradable hydrogels with readily tunable mechanical properties were formed and optimized for sustained delivery of the BTZ-loaded micelles through ionic coacervation between phenylboronic acid-functionalized polycarbonate/poly(ethylene glycol) (PEG) 'ABA' triblock copolymer and a cationic one having guanidinium- or thiouronium-functionalized polycarbonate as 'A' block. In vitro release study showed pH dependence in BTZ release. At pH 7.4, BTZ release from the micelle/hydrogel composite remained low at 7%, while in an acidic environment, ~ 85% of BTZ was released gradually over 9 days . In vivo studies performed in a multiple myeloma MM.1S xenograft mouse model showed that the tumor progression of mice treated with BTZ-loaded micelle solution was similar to that of the control group, while those treated with the BTZ-loaded micelle/hydrogel composite resulted in significant delay in tumor progression. The results show that this hydrogel has great potential for use in subcutaneous and sustained delivery of drug-loaded micelles with superior therapeutic efficacy.