Merging Experimental Design and Nanotechnology for the Development of Optimized Simvastatin Spanlastics: A Promising Combined Strategy for Augmenting the Suppression of Various Human Cancer Cells

Abstract

Simvastatin (SMV) is an antihyperlipidemic agent that has been investigated as a possible anti-cancer agent. An obstacle to malignant tumor therapy using drugs is the delivery of adequate levels to the cancer cells while minimizing side effects following their systemic administration. To circumvent this challenge, the researchers directed towards the field of nanotechnology to benefit from the nano-size of the formulation in passively targeting the tumor cells. Thus, our study aimed at investigating the potential of a combined mixture–process variable design for optimization of SMV spanlastics (SMV-SPNs) with minimized particle size and maximized zeta potential to enhance the anticancer activity of the drug. The study investigated the effects of Span® 20 and Tween® 80 as mixture components and sonication time as a process variable on particle size, polydispersity index, and zeta potential as responses. SPNs were prepared using an ethanol injection method. Combining the predicted optimized variables’ levels is supposed to achieve the set goals with a desirability of 0.821. The optimized spanlastics exhibited a measured globule size of 128.50 nm, PDI of 0.329, and ZP of −29.11 mV. The percentage relative error between predicted responses and the observed ones were less than 5% for the three responses, indicating the optimization technique credibility. A significant improvement in the cytotoxicity of the optimized formulation against three different cancerous cell lines was observed in comparison with SMV. The inhibitory concentration (IC50) values of MCF-7, HCT-116, and HEPG2 were found to be 0.89, 0.39, and 0.06 μM at 24 h incubation. The enhanced cytotoxicity could be assigned to the possible improved permeation and preferential build-up within the cancerous cells by virtue of the minimized size. These findings imply that SMV-SPNs could be an ideal strategy to combat cancer.

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“…The ratio of signal to noise was measured with adequate precision to guarantee that this model can be used to navigate the design space. A ratio greater than four is preferred [ 57 ] which was observed for all responses as shown in Table 1 .…”

Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization, in-vitro, ex-vivo, and in-vivo studies evaluation

“…Moreover, adequate precision was noticed to be higher than the desired value (4) for Y1, Y2, Y3, and Y4. Therefore, this model could be suitable for the design space navigation (Badr-eldin et al, 2022 ), whereas the fitted model was an Analysis of variance table partial sum of squares—type III for all responses.…”