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Preparation and evaluation of poly(caprolactone fumarate) nanoparticles containing doxorubicin HCl

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Author(s): N Shokri | H Akbari Javar | Sh Fouladdel | A Khalaj | MR Khoshayand | R Dinarvand | F Atyabi | A Nomani | E Azizi

Journal: DARU : Journal of Pharmaceutical Sciences
ISSN 1560-8115

Volume: 19;
Issue: 1;
Start page: 12;
Date: 2011;
Original page

Keywords: PCLF nanoparticles | Copolymer molecular weight | Nanoprecipitation method

ABSTRACT
Background and the purpose of the study: Biodegradable Poly(caprolactone fumarate) (PCLF) has been used as bioresorbable sutures. In this study, doxorubicin HCl (Dox) loaded PCLF nanoparticles were prepared and characterized.  Materials and methods: PCLFs were synthesized by polycondensation of PCL diols (Mws of 530, 1250 and 2000) with fumaryl chloride. The degradation of PCLF in NaOH, water and phosphate buffer saline (PBS), was determined in terms of Mw. Nanoparticles (NPs) were prepared by two methods. In microemulsion polymerization method, dichloromethane containing PCLF and photoinitiator were combined with the water containing surfactants and then placed under light for crosslinking. In nanoprecipitation method, the organic solvent containing PCLF was poured into the stirring water. The effect of several variables concentration of PCLF, poly vinyl alcohol (PVA), Dox and Trypan blue (Trb) and the Mw of PCLF and PVA) on NP size and loading were evaluated. Results: PCLF 530, 1250 and 2000 in PBS or water were not degrade over 28 days. Nanoprecipitaion method gave spherical (revealed by SEM images) stable NPs of about 225 with narrow size distribution and a zeta potential of -43 mV. The size of NP increased significantly with increase in Mw or concentration of PCLF. Although PVA was not necessary for formation of NPs but decreased the NP size. Dox loading and EE were 2.5-6.8% and 15-20%, respectively. Increasing the drug concentration, increased the drug loading (DL) and NP size. The entrapment efficiency (EE) for Trb ranged from 1% for PCLF530 to 6% for PCLF2000. An increase in PCLF concentration resulted in an increase in EE. Dox and Trb release showed a burst followed by 80% and 78% release during 3 and 4 days respectively.                                                                                                             Conclusion: PCLF possessed suitable characteristics for preparing nanoparticulate drug delivery system including desired NP size, stability and degradation time. Although PCLF530 NPs were the smallest, their DL was lower than PCLF1250 and 2000 NPs.
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