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 (PBA) in BTZ and catechol, and these drug-loaded micelles were i...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2018-04, Vol.10 (16), p.13274-13282
Main Authors: Lee, Ashlynn L. Z, Voo, Zhi Xiang, Chin, Willy, Ono, Robert J, Yang, Chuan, Gao, Shujun, Hedrick, James L, Yang, Yi Yan
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents
Drug Carriers
Hydrogels
Mice
Micelles
Nanoparticles
Polyethylene Glycols
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Summary: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 (PBA) in BTZ and catechol, and these drug-loaded micelles were incorporated into hydrogels to form micelle/hydrogel composites. 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 PBA-functionalized polycarbonate/poly­(ethylene glycol) (PEG) “ABA” triblock copolymer and a cationic one having guanidinium- or thiouronium-functionalized polycarbonate as “A” block. An in vitro release study showed the pH dependence in BTZ release. At pH 7.4, the BTZ release from the micelle/hydrogel composite remained low at 7%, whereas 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, whereas those treated with the BTZ-loaded micelle/hydrogel composite resulted in significant delay in the tumor progression. The results demonstrate that this hydrogel has great potential for use in subcutaneous and sustained delivery of drug-loaded micelles with superior therapeutic efficacy.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.7b14319