Development of nanostructured lipid carriers as a promising tool for methotrexate delivery: physicochemical and in vitro evaluation

Abstract

The aim of the present study is to fabricate the stable nanostructured lipid carriers (NLCs) using biocompatible excipients for the encapsulation of Methotrexate (MTX), a chemotherapeutic agent for breast cancer treatment. MTX has restricted clinical applications owing to its low solubility, non-specific targeting and adverse side effects. Glyceryl Monostearate (GMS) and Miglyol 812 (MI1) were chosen as solid and liquid lipids, respectively, for the fabrication of NLCs, and the influence of variation of solid and liquid composition was investigated. The prepared NLCs exhibited long-term stability and spherical shape morphology as characterized by electron microscopy. The internal structure of fabricated NLCs was arranged into cubic crystalline as confirmed by small-angle X-ray scattering (SAXS) analysis. MTX's encapsulation efficiency of ∼85 ± 0.9%. and sustained in vitro release of MTX ∼ 52% ± 3.0 in 24 h was achieved. Classical molecular dynamics (MD) simulations were performed to study the structural stability of the MTX encapsulated NLCs. Hemolysis carried out on the NLCs showcased the biosafety of the formulation under the tolerance limit (<10%). Further, the MTT assay demonstrates that MTX-loaded NLCs exhibited toxicity against HeLa and MCF-7 cell lines as compared to blank NLCs. The finding demonstrates NLCs as promising vehicles for MTX delivery to address cancer.

Communicated by Ramaswamy H. Sarma

Graphical abstract

Keywords:

• Nanostructured lipid carriers
• methotrexate
• SAXS studies
• In vitro release
• molecular dynamics simulation

Acknowledgments

Jyoti Rathee acknowledges UGC, New Delhi for the Senior Research Fellowship (SRF). Rohini Kanwar acknowledges Mehr Chand Mahajan DAV College for Women and PU for support. Surinder Kumar Mehta acknowledges DST-PURSE II and Deepak B. Salunke is thankful to DBT New Delhi for the Ramalingaswami fellowship award. Sandip V. Pawar acknowledges UGC Start-up Grant No. F.4-5(65-FRP) (lv-cycle)/201 7(BSR) under UGC Faculty Recharge Programme UGC, New Delhi for financial support. SAIF/CIL of Panjab University is gratefully acknowledged. Shikha Sharma acknowledges Institute of Nano Science and Technology (INST) for the fellowship support. Md. Ehesan Ali acknowledges the financial support from the Department of Science and Technology through SERB-ECR Project No. ECR/2016/000362 and Indo-Sweden joint Project No. DST/INT/SWD/VR/P01/2016.

Disclosure statement

No potential conflict of interest was reported by the authors.