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Rapamycin-loaded, capryol� 90 and oleic acid mediated nanoemulsions: Formulation development, characterization and toxicity assessment
Authors
R. Aboofazeli
N. Nafissi-Varcheh
+4 more
S.N. Ostad
A. Shafaati
H. Sobhani
P. Tarighi
Publication date
1 January 2018
Publisher
Abstract
This study was planned to explore the capability of nanoemulsions (NEs) consisting of Capryol� 90 and oleic acid for the delivery of rapamycin (RAP). Permeability and cytotoxicity of RAP-loaded NEs were also inspected. Pseudo-ternary phase diagrams were created with oleic acid and Capryol� 90 (as oil phase) and four surfactants and co-surfactants at various weight ratios (Rsm). Selected NEs from O/W region on the phase diagrams with the drug concentration of 1 mg/mL, were prepared via the spontaneous emulsification technique, characterized for particle size and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release was determined for a period of 48 h using a dialysis sac. The assay of RAP was determined using HPLC technique. Cytotoxicity of NEs was evaluated by MTT assay on breast cancer cell line, namely SKBR-3. The permeability of RAP-loaded NEs across Caco-2 monolayers was assessed by measurement of TEER (transepithelial electrical resistance) value. The intracellular uptake of coumarin 6-loaded NEs by SKBR-3 cells was also investigated using florescence microscopy. NEs containing oleic acid/Tween 20/propylene glycol, Capryol� 90/Tween 20/iso-propanol, and Capryol� 90/Cremophor® RH40/Transcutol® P showed more cytotoxicity and permeability compared with the RAP methanolic solution. The minimum toxic concentration of RAP in NE formulations was found to be 7.5 µg/mL. The highest intracellular uptake was observed for the NE composed of Capryol� 90/Tween 20/iso-propanol which was in consistent with the results obtained from cytotoxicity and permeability tests. The overall results implicated that this novel carrier was effective for enhancing RAP permeation in Caco-2 cell membrane along with enhancement of cytotoxicity. © 2018, Iranian Journal of Pharmaceutical Research. All rights reserved
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oai:eprints.iums.ac.ir:6592
Last time updated on 10/10/2019