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Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy
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Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy
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Journal Article
Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy
2020
Overview
Docetaxel (DTX) was loaded in nanoliposomes based on a new remote loading method using mannitol and acetic acid as hydration buffer. DTX loading conditions were optimized, and the final formulations were prepared according to the best parameters which were HSPC/mPEG2000-DSPE/Chol (F1), HSPC/mPEG2000-DSPE/DPPG/Chol (F2), HSPC/mPEG2000-DSPE/DSPG/Chol (F3), at molar ratios of 85/5/10, 80/5/5/10, 80/5/5/10, respectively. DTX-liposomes were found of desired size (~115 nm) and homogeneity (PDI ≤ 0.2), high drug encapsulation efficacy (34–67%) and DTX concentration, and favorable stability. Passive loaded counterparts liposomes showed three times lower encapsulation efficacy compared to the remote loaded liposomes. The drug release of remote loaded liposomes in plasma 50% was significantly more controlled and less in comparison with their passive loaded counterparts (p < 0.0001). The IC50 values of formulations were determined on MCF-7, 4T1, TUBO, NIH/3T3 cell lines. The biodistribution of iodinated docetaxel as free or liposomal form exhibited significantly greater accumulation of DTX-liposomes in tumors than that of free docetaxel due to the EPR effect.
In vivo
experiment with BALB/c mice bearing 4T1 or TUBO breast carcinoma tumors also showed that DTX-liposomes could significantly delay tumor growth and prolonged the survival time in comparison with control and Taxotere groups at the similar dose of 8 mg/kg. F1 and F2 formulations were stable and showed good anti-tumor activity and merit further investigation.
Publisher
Nature Publishing Group UK
Subject
/ Animals
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ Breast Neoplasms - drug therapy
/ Cell Proliferation - drug effects
/ Chemistry, Pharmaceutical - methods
/ Drug Liberation - drug effects
/ Female
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Rats
/ Science
