Cytotoxicity and pharmacokinetics study of nanostructured lipid carriers of mechlorethamine: Preparation, optimization and characterization

Abstract

The present work was aimed to prepare, optimize and characterize nanostructured lipid carriers (NLCs) loaded with mechlorethamine for improvement in pharmacokinetics. Emulsification-ultrasonication method was used to formulate nanostructured lipid-based carriers. 3D-response surface methodology helped to explore the qualitative and quantitative relationship. Optimization was done by Box–Benhken design and response surface methodology using Stat–Ease design expert software. NLCs were spherical, non-aggregates with average size of 105.92 ± 1.04 nm and dispersity index 0.02; potential was around −30.1 ± 0.82 mV. The percentage entrapment efficiency and loading capacity of optimized NLCs was 91.7 ± 1.20% and 1.79 ± 0.11%, respectively. DSC revealed that the drug existed in amorphous form in NLCs. In-vitro cumulative percentage release study exhibited bi-phasic response. In case of NLCs; T_max was achieved at 37.5 ± 0.56 min with a sharp increase in plasma level [C_max value 0.62 ± 1.07 µg/ml]. The IC50 value was found to be 39.087 ± 0.13 and 21.39 ± 0.17 μM for pure mechlorethamine and NLCs, respectively. Nano-lipid carriers are prominent system for achieving delivery of cytotoxic nitrogen mustard drugs with improved therapeutic efficiency.

Keywords:

• Mechlorethamine
• nano-lipid carriers
• emulsification-ultrasonication
• pharmacokinetics
• MTT assay
• response surface methodology
• cancer

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgments

The author acknowledges the facilities provided by the Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari, Durg (C.G.). One of the authors, BG, is thankful to her supervisor for timely support and guidance throughout the study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors thank and acknowledge DST-SERB (Science & Engineering research board) New Delhi for providing financial assistance under NPDF Scheme (national post-doctoral fellowship) to complete this research work. Ref. No PDF/2016/002629.