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Development and in Vitro/In Vivo Evaluation of a Novel Targeted Polymeric Micelle for Delivery of Paclitaxel Publisher Pubmed



Emami J1 ; Rezazadeh M1 ; Hasanzadeh F2 ; Sadeghi H3 ; Mostafavi A1 ; Minaiyan M4 ; Rostami M2 ; Davies N5
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran
  2. 2. Department of Medical Chemistry, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran
  3. 3. Department of Biotechnology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran
  4. 4. Department of Pharmacology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran
  5. 5. Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada

Source: International Journal of Biological Macromolecules Published:2015


Abstract

In this study a novel receptor-targeted micelle delivery system based on tocopherol succinate-chitosan-polyethylene glycol-folic acid (TS-CS-PEG-FA) was synthesized and loaded with paclitaxel (PTX). Physicochemical properties of the micelles such as critical micelle concentration, micelle size, entrapment efficiency, stability, release properties, cellular uptake and in vitro cytotoxicity were investigated in detail. Furthermore, the pharmacokinetics and tissue distributions of PTX-loaded micelles were evaluated in Balb/c mice and compared with Anzatax® (PTX in Cremophor EL®). Particle sizes and zeta potentials of the micelles were in the range of 162.3-277.1nm and 18.5-28.3mV, respectively. The drug entrapment efficiencies of the micelles were within 53.6-82.5% (w/w). Cytotoxicity assay demonstrated increased cytotoxic activity of PTX-loaded TS-CS-PEG-FA micelles compared to free PTX. The Vd and t1/2β of PTX-loaded TS-CS-PEG-FA were increased by 2.76- and 2.05-fold, respectively, while the plasma AUC of the micelles was only 0.76-fold lower than those of Anzatax® As demonstrated by tissue distribution, the PTX/TS-CS-PEG-FA micelles increased accumulation of PTX in tumor tissue. Therefore, the targeted chitosan derived micelle offered a stable and effective delivery system for PTX cancer chemotherapy. © 2015 Elsevier B.V..
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