Development of Polymeric Nanocarriers for Brain Targeted Delivery of Atorvastatin: A Quality-By-Design Approach

Objective: Atorvastatin (ATV) is effective in reducing total cholesterol and low-density lipoprotein levels. Furthermore, it produces pleiotropic effects in neurodegenerative conditions such as Parkinson's, Alzheimer's, and epilepsy. However, due to the effective defense system of the central nervous system (CNS), the development of new medicines for clinical conditions has proven difficult. In this context, nanotechnology was applied as a promising solution to promote drug vectorization to the brain. Methods: The solvent emulsification-diffusion method was used to develop nanoparticles (NPs) based on polylactic acid and coated with polysorbate 80 containing ATV. Quality-by-Design (QbD) was used in the optimization of nanoparticles production through the application of the experimental design Box-Behnken Design. Results: After optimizing the independent factors including sonication time, surfactant concentration and surfactant volume, the NPs presented physicochemical characteristics such as entrapment efficiency of 86.4 ± 2.4%, mean size of 225.2 ± 4.8 nm, and zeta potential of -14.4 ± 0.36 mV. In the in vitro release study, approximately 20% of the encapsulated ATV was released. Conclusion: The application of QbD was very useful in demonstrating its applicability in the nanotechnological pharmaceutical area for controlling and predicting the influence of the variables in the production of NPs. The NPs developed in this study presented adequate physicochemical characteristics, which is promising for future in vivo studies. The physicochemical characteristics included entrapment efficiency of 86.4 ± 2.4%, mean size of 225.2 ± 4.8 nm, and zeta potential of -14.4 ± 0.36 mV. In the in vitro release study, approximately 20% of the encapsulated ATV was released. The application of QbD was very useful in demonstrating its applicability in the nanotechnological pharmaceutical area for controlling and predicting the influence of the variables in the production of NPs. The NPs developed in this study presented adequate physicochemical characteristics, which is promising for future in vivo studies.