QBD-Based Optimization and Formulation of Doxorubicin Bcl-2 SIRNA-Loaded Sphingosomes

Background

By increasing drug stability and water solubility, cycle duration, rate of absorption into target cells or tissues, and reducing enzymatic degradation, Nano Drug Delivery Systems (NDDS) improve the safety and effectiveness of drugs. The Sphingosomes have better drug retention properties and are significantly more resilient to acid hydrolysis. siRNAs are mostly used to silence post-transcriptional gene expression in cancer treatment. Doxorubicin is a known anticancer drug for lung cancer.

Materials and Methods

The study shows how to use a 32 complete factorial design to optimize a bcl2 SIRNA-doxorubicin-loaded sphiongosome for the treatment of lung cancer. The drug was aimed at reducing the toxicity of the drug and in the treatment of multiple drug-resistant tumors. Nano forms of Sphingosomes were prepared using the thin film hydration process, and optimization was carried out using 3² full factorial designs in conjunction with the desirability function. Ten formulations with various drugs: lipid and sphingomyelin: cholesterol ratios were created, and their entrapment effectiveness, PDI, and vesicle size were assessed. An analysis of variance was used to determine the model’s statistical validity (ANOVA). Contoured plots and response surface graphs were used to analyze the influence of variables on responses. Entrapment effectiveness and vesicle size data were discovered to be extremely similar to the predicted values.

Results

The formulation was found to be spherical with an average diameter of 263.4 nm, PDI of 0.198, entrapment efficiency of 69.2, and -33.4 mV zeta potential. Results from TEM demonstrated the 200 nm particle size. DSC studies proved thermal peaks were in range. FTIR results of the physical mixture and the formulation were in the range and there was no physical incompatibility, According to serum stability, the formulation was resistant to nuclease digestion for 12 hr. The sterility test proved the formulation was sterile.

Conclusion

The outcomes show that the QbD technique in sphingosome creation can enhance the formulation process. The creation of the DOX siRNA sphingosome formulation can be optimized and rationalized with the use of cutting-edge design and development methodologies.