Self-Assembling Polymer Micelle/Clay Nanodisk/Doxorubicin Hybrid Injectable Gels for Safe and Efficient Focal Treatment of Cancer

The purpose of this study was to fabricate a safe and effective doxorubicin (DOX)-delivery system for focal cancer chemotherapy. A novel biodegradable injectable gel was developed through self-assembly of poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PLGA-P...

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Bibliographic Details
Published in:Biomacromolecules 2015-03, Vol.16 (3), p.880-889
Main Authors: Nagahama, Koji, Kawano, Daichi, Oyama, Naho, Takemoto, Ayaka, Kumano, Takayuki, Kawakami, Junji
Format: Article
Language:English
Subjects:
Aluminum Silicates - chemistry
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacology
Cell Survival - drug effects
Doxorubicin - administration & dosage
Doxorubicin - pharmacology
Drug Carriers - administration & dosage
Gels
HeLa Cells
Humans
Male
Mice, Inbred BALB C
Micelles
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Particle Size
Polymerization
Polymers - chemistry
Xenograft Model Antitumor Assays
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Summary:The purpose of this study was to fabricate a safe and effective doxorubicin (DOX)-delivery system for focal cancer chemotherapy. A novel biodegradable injectable gel was developed through self-assembly of poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer micelles, clay nanodisks (CNDs), and DOX. We discovered that DOX loaded in the hybrid gels acts as an anticancer drug and as a building block to organize new gel networks. Accordingly, long-term sustained release of DOX from hybrid injectable gels without initial burst release was achieved. Moreover, it was revealed that the DOX incorporated into gel networks controls its own release profile. This hybrid injectable gel is a self-controlled drug release system, which is a novel concept in controlled drug release. Importantly, a single injection of PLGA-PEG-PLGA/CND/DOX hybrid gel provides long-term sustained antitumor activity in vivo against human xenograft tumors in mice, suggesting the potential of hybrid gels as a valuable local DOX-delivery platform for cancer focal therapy.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm5017805