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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: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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