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Optimization of Docetaxel Loading Conditions in Liposomes: Proposing Potential Products for Metastatic Breast Carcinoma Chemotherapy Publisher Pubmed



Vakilighartavol R1 ; Rezayat SM1, 2 ; Faridimajidi R1 ; Sadri K3 ; Jaafari MR4, 5
Authors
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Authors Affiliations
  1. 1. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, 98451-3546, Iran
  4. 4. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  5. 5. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Scientific Reports Published:2020


Abstract

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. © 2020, The Author(s).
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