Preparation of α-Tocopherol based nanoemulsion for efficacious delivery of Methotrexate

Abstract

The present work dwells upon developing and assessing the efficacy of nanoemulsion (NEm) for Methotrexate (MTX) delivery. Herein, MTX-loaded NEm was prepared using the ultrasonic nano emulsification method by exploiting biocompatible excipients such as α-Tocopherol, Miglyol 812, Tween 80, and ethanol. Employing ultrasonic nano emulsification processes leads to the preparation of NEm with smaller droplet sizes and uniform distribution. The physicochemical characterization by transmission electron microscopy confirmed that the blank NEm and MTX-loaded NEm possesses spherical-shaped nano range particles and drug might be present within the droplet or on the surface of the nanoemulsion. The encapsulation efficiency of MTX in NEm was estimated as 52 ± 0.6%. The recorded cumulative in-vitro release was 54.74 ± 2.73% in 24 h and using kinetic modeling, its Fickian diffusion release was validated. Higher stability (94.16 ± 1.51%) and bioaccessibility (96.06 ± 1.01%) of MTX-loaded NEm were also confirmed. The hemolysis profile was under the tolerance limit (<8%) for all the concentrations of the formulation. The cell viability assay of NEm loaded with MTX showed significant toxicity against the MCF-7 and HeLa cell lines which validated MTX-loaded NEm as a biosafety vehicle.

Graphical Abstract

Keywords:

• Nanoemulsion
• Methotrexate
• in-vitro release
• bioaccessibility
• cytotoxicity

Acknowledgments

Jyoti Rathee acknowledges UGC, New Delhi for the Senior Research Fellowships (SRF). Surinder Kumar Mehta acknowledges DST-PURSE II and Deepak B. Salunke is grateful to DBT New Delhi for the award of the Ramalingaswami fellowship. Sandip V. Pawar acknowledges financial support from the UGC Start-up grant No.F.4-5(65-FRP) (lv-cycle)/201 7(BSR) under UGC Faculty Recharge Programme UGC, New Delhi. Sophisticated Analytical Instrumentation Facility (SAIF) of Panjab University is gratefully acknowledged.

Authors’ contributions

The present research idea of ‘Development and Physicochemical evaluation of biocompatible nanoemulsion as a potential drug delivery system’ was conceived by Jyoti Rathee under the supervision of Prof. S. K. Mehta and Dr. Deepak B. Salunke. The basic characterizations, synthesis and analysis was conducted by Jyoti Rathee and Rohini Kanwar. Further, the biological analysis (Hemolysis and cell viability studies) were performed by Dr. Sandip V. Pawar with the help of Laxmi Kumari. All authors read and approved the final manuscript. Prof. S.K.Mehta supervised and helped in the implementation of the experiments.