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Preparation and Characterization of Spray-Dried Inhalable Powders Containing Polymeric Micelles for Pulmonary Delivery of Paclitaxel in Lung Cancer Publisher Pubmed



Rezazadeh M1 ; Davatsaz Z2 ; Emami J2 ; Hasanzadeh F2 ; Jahaniannajafabadi A3
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Pharmacy and Pharmaceutical Sciences Published:2018


Abstract

Purpose: Local delivery of chemotherapeutic drugs to the lungs offers many advantages for lung cancer treatment compared to conventional systemic chemotherapy. In the present study, novel mixed polymeric micelles based on tocopheryl succinate-polyethylene glycol 1000 and 5000 Da (TPGS 1K and TPGS 5K ) were synthesized and loaded with paclitaxel (PTX). Then, the optimized micelles were incorporated as colloidal drug delivery system into lactose carrier particles using a spray drying technique. Methods: The mixed micelles of TPGS 5K and TPGS 1K in different molar ratios (10:0, 7:3, 5:5, 3:7, 0:10) were prepared and physicochemical properties including: particle size, zeta potential, critical micelle concentration (CMC), drug loading, drug release rate, and in vitro cytotoxicitywere investigated in details. The optimized nanoparticles were co-spray dried with lactose carriers to produce the spherical particle morphology of the inhalable particles. Results: Particle sizes and zeta potentials of the different formulations varied in the range of 102 to 196 nm and-9.4 to-13.8 mV, respectively. The lowest CMC values were calculated for 5:5 and 7:3 combinations (16.33 and 17.89 µM, respectively). The drug release rate from different formulations were very slow and only 30% of the drug was released during 72 h. Cytotoxicity assay demonstrated increased cytotoxic activity of PTX-loaded mixed micelles compared to the free drug. The in vitro deposition data indicated that spray drying of PTX-loaded micelles with lactose resulted in the production of inhalable powders with the high fine particle fraction (60%). Conclusion: These results demonstrate that this novel PTX-loaded micelles embedded in dry powder inhalation aerosol platform has a great potential to be used in lung cancer treatment. © 2018, Canadian Society for Pharmaceutical Sciences. All rights reserved.
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