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

Abstract

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.

Development of silver nanoparticle-based hydrogel composites for antimicrobial activity

“…Hydrogels are 3-dimensionally interconnected hydrophilic polymers, which can absorb an extensive amount of water within the structures without being dissolved in water. Since the chemical, electrical, and mechanical properties of polymer hydrogels could be quite analogous with those present in biological tissues, there have been extensive efforts to utilize the hydrogels in biological applications such as drug delivery (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), wound/burn dressing (13,14), scaffolds for tissue engineering (15)(16)(17), and others (18)(19)(20)(21). In particular, the inclusion of drugs inside polymer hydrogels may represent an innovative drug delivery system because the release rate of the loaded drugs can be regulated by external stimuli (1,2,(4)(5)(6)(7)(8)(9).…”

“…In many cases, the change in pH (2,3), temperature (1,7,9), and light (4) has triggered the swelling, shrinkage, or degradation of the hydrogels to release the drugs in a controlled way. Alternatively, in the absence of the external stimuli, the slow diffusion nature of the drug release can ensure a constant delivery as well as prolonged duration of drugs, which is necessary for exerting long-term efficacy (10)(11)(12).…”

Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery

“…Besides, fewer cells with normal nuclei morphology were observed in the group treated with DTX/XNMs in comparison with cells treated with DTX/NNMs or DTX/LNMs, which, qualitatively, certified that DTX/XNMs could promote the apoptotic progress of A2780 cells. 45 …”

Structures and Applications of Thermoresponsive Hydrogels and Nanocomposite-Hydrogels Based on Copolymers with Poly (Ethylene Glycol) and Poly (Lactide-Co-Glycolide) Blocks

“…We also revealed excellent cell compatibility from hemolysis assay and cell culture test on and in the hydrogels. Then, in 2015, Nagahama et al reported on a delivery system for DOX from thermoresponsive nanocomposite hydrogels (Figure 7b) [65], revealing that DOX worked as a crosslinking agent. They also revealed that long-term sustained release of DOX from thermoresponsive nanocomposite hydrogels without initial burst release could be achieved.…”