Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 84, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2023.104509
Keywords
Cisplatin; Thermoresponsive liposomes; In -vivo lung carcinoma; Diethylnitrosamine; Ovarian cancer; Breast cancer
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Thermoresponsive liposomes loaded with cisplatin (CDDP@TSLs) were developed and characterized for enhanced anticancer efficacy. The results showed that CDDP@TSLs exhibited greater cytotoxicity against various cancer cells at 39℃ and higher cellular uptake at tumor sites. In a mouse model of lung carcinoma, CDDP@TSL treatment demonstrated good therapeutic effect. The developed CDDP@TSLs may provide an enhanced anticancer efficacy and minimize systemic toxicities.
Thermoresponsive drug delivery systems have been used previously to deliver chemotherapeutic agents to tu-mors in a hyperthermic microenvironment. The objective of the present study was to fabricate and characterize Cisplatin-loaded thermoresponsive liposomes (CDDP@TSLs) for enhanced anticancer efficacy. CDDP@TSLs were prepared by a thin-film hydration method with varied ratios of dipalmitoyl phosphatidylcholine and hydroge-nated soy phosphatidylcholine, and fixed amounts of distearyl phosphoethanolamine polyethylene glycol2000 and Cisplatin. The prepared CDDP@TSLs had a particle size of up to 201.8 nm, surface a charge of-6.31 mV, high entrapment efficiency of Cisplatin, and thermoresponsive release behavior. The CDDP@TSLs were tested in vitro for cytotoxicity against A549 cells (lung carcinoma), SKOV-3 cells (ovarian cancer) and MDA-MB-231 cells (breast adenocarcinoma) at 37 degrees C and 39 degrees C since the temperature at tumorous sites can be higher than at normal sites. The results with CDDP@TSLs showed greater cytotoxicity at 39 degrees C. Cellular uptake studies displayed a many-fold uptake of the particles by the various cell types and their enhanced internalization at tumor sites. In lung carcinomas induced in albino mice by diethylnitrosamine, healing by CDDP@TSL treatment indicated the efficacy of the thermoresponsive liposomal formulation. The developed CDDP@TSLs may provide an enhanced anticancer efficacy that may maximize the therapeutic effect and minimize the systemic off-site toxicities.
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