Application of Design Of Expert for the Development and Systematic Optimisation of L-Asparaginase loaded Nanoparticulate Carrier Drug Delivery Systems
L-Asparaginase (L-ASN) is a clinically approved chemotherapeutic agent for the treatment of acute lymphoblastic leukaemia and lymphosarcoma. The aim of this research study was to develop and to optimize solid lipid nanoparticle formulation loaded with enzyme L-Asparaginase using response surface methodology (RSM) . The formulation was prepared by a modified double emulsion method followed by solvent evaporation technique using a combination of high-speed homogeniser (10000 rpm) and an automatic hotplate for a temperature 40°C. Box-Behnken Design (BBD) was involved in the study to establish and to understand the relationship between selected design factors and the experimental data thus obtained. A set of 29 formulations were prepared in triplicate based on the recommendations of BBD. The desired results obtained were found to be in close agreement with the experimental results. The responses were ﬁtted to a quadratic; polynomial model. The statistical validation using Analysis of Variance (ANOVA) was done for the respective fitted models. Response Surface Graphs and 3D contour plots were constructed to understand the effect of independent variables in different combinations on the desired responses. SLN prepared were found to be spherical in shape and the mean particle size ˂198 nm. The polydispersity index (PDI) and the zeta potential recorded for the prepared formulation corresponding to the particle size was 0.096 ± 0.043 and −10.39 mV respectively. The enzyme drug loading was 10.11% ± 2.02 and the enzyme entrapment efficiency was found to be 76.19% ± 1.23. BBD found to be very effective in considering the effects of independent formulation variables to develop an optimised enzyme loaded SLN formulation with sufficient activity of the L-ASN enzyme.
Keywords: Solid Lipid Nanoparticle, Response Surface Methodology, Box-Behnken Design
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