Formulation Development and Toxicity Assessment of Triacetin Mediated Nanoemulsions as Novel Delivery Systems for Rapamycin

Document Type: Research article

Authors

1 Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences

2 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences

3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences

4 Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences

5 Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences

6 Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti Uni. Med. Sci.

Abstract

The aim of this investigation was to design and develop nanoemulsions as novel delivery systems for rapamycin. Phase behavior of quaternary systems composed of Traicetin (as oil), various surfactants and co-surfactants and water at different surfactant/co-surfactant weight ratios were investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region of the phase diagrams, depending upon the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 1 mg/mL of the drug. The NEs were characterized and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release from the selected formulations were determined for a period of 48 hr, using a dialysis sac. Assay of rapamycin was carried out using an HPLC technique. The effect of NEs on the viability of SKBR-3 cells was evaluated by MTT assay. The integrity of Caco-2 cell monolayers was measured by Transepithelial Electrical Resistance (TEER) and the transport of rapamycin-loaded NEs across Caco-2 cell monolayers was then assessed. The uptake of NEs by SKBR-3 cells was also investigated using florescence microscopy. Maximum drug release was observed in case of 4 formulations prepared with Tween 80 and Tween 20. MTT test results revealed different toxicity of NEs for SKBR-3 cell line and TEER demonstrated that formulations containing Tween 20 caused more considerable decrease in cell integrity in comparison with those prepared with Tween 80. The results obtained from cellular uptake experiments were in consistent with those obtained from TEER and cytotoxicity experiments.

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