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Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel: A dual approach for in situ treatment of tumors.

ABSTRACT: The in situ gelling hybrid hydrogel system has been reported to effectively concentrate chemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles (docetaxel-loaded mixed micelles) are able to increase the solubility of DTX in water, and then a high drug loading rate of hydrogels can be achieved by encapsulating the docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature of DTX-MM-hydrogels (thermosensitive hydrogels incorporated with docetaxel-loaded mixed micelles) can accelerate the formation of a depot of this drug-loaded system at the site of administration. Therefore, the hydrogels provide a much slower release compared with DTX-micelles and DTX-injection. An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in vivo trials have shown that the DTX-MM-hydrogels have a higher antitumor efficacy and systemic safety. In conclusion, the DTX-MM-hydrogels prepared in this study have considerable potential as a drug delivery system, with higher tumor inhibition effects and are less toxic to normal tissues.

SUBMITTER: Xu M

PROVIDER: S-EPMC7032140 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel: A dual approach for <i>in situ</i> treatment of tumors.

Xu Meng M Mou Yanhua Y Hu Mingming M Dong Wenxiang W Su Xitong X Wu Rongxia R Zhang Peng P

Asian journal of pharmaceutical sciences 20180615 4

The <i>in situ</i> gelling hybrid hydrogel system has been reported to effectively concentrate chemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles (docetaxel-loaded mixed micelles) are able to increase the solubility of DTX in water, and then a high drug loading rate of hydrogels can be achieved by encapsulating the docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature of DTX-MM-hydrogels (thermosensitive hydrogels incorpora ...[more]

PMID: 32104411

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Project description:PurposeOsteosarcoma is considered as the most common primary malignant bone tumor in children and adolescents, and the treatments including chemotherapy and surgery were far from satisfactory. Localized tumor treatments by hydrogels incorporating combined chemotherapeutic drugs have recently emerged as superior approaches for enhanced anti-tumor effects and reduced systemic toxicity.MethodsA novel injectable thermosensitive poly (lactide-co- glycolide)-poly (ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer hydrogel containing doxorubicin and cisplatin for the localized chemotherapy of osteosarcoma were synthesized and characterized. The in vitro drug release properties of the drugs-loaded hydrogels were investigated. To study the anti-tumor efficacy of hydrogels depots in vitro, the cytotoxicity and apoptosis rate against Saos-2 and MG-63 cells were evaluated by MTT, Annexin V and PCR methods. The in vivo synergistic anti-tumor efficacy of the multi-drugs co-loaded hydrogels was investigated by human osteosarcoma xenografts. Additionally, the systemic toxic side effects were evaluated by ex vivo histological analysis of the major organs of the mice.ResultsThe PLGA-PEG-PLGA copolymer solution underwent a sol-gel transition at appropriate temperature and degraded in the PBS, presenting a friendly biocompatibility in vitro. The in vitro cell viability tests demonstrated that DOX and CDDP co-loaded hydrogels exhibited synergistic anti-proliferation effect, due to the sustained release of drugs from the drugs-loaded hydrogel. The treatment with DOX and CDDP co-loaded hydrogel led to the highest efficiency in inhibiting the tumor growth, enhanced tumor necrosis rate and increased regulation of the apoptosis-related gene expressions, indicating a synergistic anti-tumor efficacy in vivo. Additionally, ex vivo histological analysis of the nude mice exhibited low systemic toxicity.ConclusionThe combination treatment of osteosarcoma by localized, sustained co-delivery of DOX and CDDP by PLGA-PEG-PLGA hydrogel may serve as a promising strategy for efficient clinical treatment of osteosarcoma.

Project description:Endophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxis after cataract surgery. This procedure is controversial because of both the low efficacy and the low adherence to therapy by elderly patients. A unique slow release antibiotic intravitreal injection could solve these problems. The objective of the present study was to design ophthalmic nanocomposite delivery systems based on in situ gelling formulations that undergo sol-to-gel transition upon change in temperature to prolong the effect of CEF. Oil in water (O/W) microemulsion (µE) and solid lipid nanoparticles (SLN), obtained with an innovative formulation technology called cold microemulsion dilution, were evaluated as ocular drug delivery systems for CEF. Drug entrapment efficiency up to 80% was possible by esterifying CEF with 1-dodecanol to obtain dodecyl-CEF (dCEF). Both dCEF-loaded SLN and µE were then added with Pluronic®F127 (20% w/v) to obtain a nanocomposite hydrogel-based long acting system. The prepared thermosensitive formulations were evaluated for their physical appearance, drug content, gelation temperature, injectability and rheological properties, in vitro release studies and stability studies. Moreover, cell proliferation assays on human retinal pigment epithelial ARPE-19 cells were performed to evaluate the influence of this innovative system on the cellular viability. In addition, minimal inhibitory concentration (MIC) was assessed for both CEF and dCEF, revealing the need of dCEF hydrolysis for the antimicrobial activity. Although further experimental investigations are required, the physico-chemical characterization of the nanocomposite hydrogels and the preliminary in vitro release studies highlighted the potential of these systems for the sustained release of CEF.

Dataset Information

Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel: A dual approach for in situ treatment of tumors.

Publications

Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel: A dual approach for <i>in situ</i> treatment of tumors.

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