Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box-Behnken design.
The treatment of brain cancer remains one of the most difficult challenges in oncology. The purpose of this study was to develop transferrin-conjugated nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX). PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the impact of various formulation variables were assessed using Box-Behnken design. Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro cytotoxicity of it was investigated against U-87 brain cancer cell line. As a result, 14.1 mg of cholesterol, 18.5 mg of triolein, and 0.5% poloxamer were used to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted formulation were confirmed to be 205.4 ± 11 nm, 25.7 ± 6.22 mV, 91.8 ± 0.5%, 5.38 ± 0.03% and 29.3 h, respectively. Following conjugation of optimized PTX-NLCs with transferrin, coupling efficiency was 21.3 mg transferrin per mmol of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non-significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could potentially be exploited as a delivery system in brain cancer cells.
a Department of Pharmaceutics and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Islamic Republic of Iran.
Jaber
J
Emami
b Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Islamic Republic of Iran.
Mahboubeh
M
Rezazadeh
c Department of Medicinal Chemistry and Isfahan Pharmaceutical Research Center, School of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Islamic Republic of Iran.
Hojjat
H
Sadeghi
a Department of Pharmaceutics and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Islamic Republic of Iran.
Khashayar
K
Khadivar
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008962:Models, Theoretical; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000379:methods*; D014168:Transferrin / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008055:Lipids; D014168:Transferrin; D017239:Paclitaxel
BBB; NLC; PTX; cancer