Title:Folic acid Targeted Polymeric Micelles Based on Tocopherol Succinate- Pulluan as an Effective Carrier for Epirubicin: Preparation, Characterization and In-vitro Cytotoxicity Assessment
Volume: 15
Issue: 2
Author(s): Farshid Hassanzadeh, Mozhdeh Mehdifar, Jaleh Varshosaz, Ghadam Ali Khodarahmi and Mahboubeh Rostami*
Affiliation:
- Novel Drug Delivery Systems Research Centre and Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan,Iran
Keywords:
Pullulan, polymeric micelles, targeted drug delivery, folic acid, -tocopherol succinate, epirubicin (EPI).
Abstract: Background: Chemotherapy still encounters a serious drawback, the lack of selectivity of
anticancer drugs toward neoplastic cells, thus, the normal cells are affected by the cytotoxic action of
the drugs. This causes a narrow therapeutic index in most anticancer drugs.
Objective: We describe the preparation of pullulan-tocopherol succinate-folic acid (Pu-TS-FA) micelles
for the first time to targeted delivery of Epirubicin (EPI) to Hela and MCF-7 cell lines.
Methods: We confirmed the structure of conjugate using spectroscopic methods. The degree of substitution
for both folic acid and tocopherol succinate was calculated using 1HNMR. We prepared the micelles
via direct dissolution method. All the physicochemical properties of micelles including size, zeta
potential, polydispersity index (PDI), critical micelle concentration (CMC), entrapment efficiency (EE
%) and release efficiency (RE24%) were determined. The morphology of particles was studied using
transmission electron microscopy (TEM), and the in-vitro cell cytotoxicity of EPI loaded micelles was
studied using MTT assay on MCF-7 and Hela cell lines.
Results: The optimized micelles showed the particle size of 149.5 nm, the zeta potential of -6.49 mV, a
polydispersity index of 0.259 ± 0.07, LE% of 88 %, and RE24% of 63 ± 2.45 % with a relatively low
CMC 194.87 µg/ml. TEM showed the relatively uniform spherical structure for particles and in vitro
MTT assay showed that EPI loaded micelles were more toxic on Hela cell line than MCF7 as expected.
Conclusion: Since the Pu-TS-FA micelle could improve the anticancer activity of epirubicin and would
be a promising candidate for EPI treatment of cancers.
