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; Tmax was achieved at 37.5 ± 0.56 min with a sharp increase in plasma level [Cmax 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.
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