Synthesis and Encapsulation of Antidepressants in Biodegradable Polymeric, Lipid Nanoparticles to bypass the Blood Brain Barrier

The main objective of this research is to study the encapsulation and release of antidepressants using different nanoparticle platforms that have the potential to reach the blood-brain barrier (BBB). Depression is a mental health illness related to a mood disorder formed by a persistent feeling of sadness and losing interest in an individual's daily activities. The blood-brain barrier is a network of brain microvascular endothelial cells (BMVEC) that guards the brain against toxic substances in the blood, provides the brain with sufficient nutrients, and filters unhealthy substances from the brain into the blood. In this work, different nanoparticles particularly polylactic glycolic acid (PLGA) and liposomes composed of two phospholipids, dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylethanolamine (DMPE), and Cholesterol (CHOL) were formulated and studied. The antidepressants used in this study include paroxetine and venlafaxine. Paroxetine and venlafaxine are antidepressants used to treat depression, anxiety, and obsessive-compulsive disorder. Some issues encountered when antidepressants are ingested include the drug concentration's inability to reach the brain due to the blood-brain barrier and the low bioavailability in the first-pass metabolism. Paroxetine was encapsulated in PLGA, liposomes, and liposomes containing polyethylene glycol (PEG) as an excipient (Liposomes/PEG), and a high loading of the drug was obtained. Similarly, venlafaxine was incorporated into liposomes and liposomes/PEG. Based on the literature, these nanoparticles have been able to bypass the BBB and release the drug loading effectively. Standard curves of absorbance-concentration of paroxetine and venlafaxine were obtained. Similar standard curves were determined with paroxetine /PEG and venlafaxine /PEG. The particle sizes and zeta potentials of all the nanoparticle preparations were characterized using dynamic light scattering analysis. The entrapment efficiencies of all the encapsulated drug preparations were evaluated to determine the amount of successfully encapsulated drugs. In vitro drug release studies were performed using in all cases a dialysis approach to measure concentration release profiles of the drugs leaving the nanoparticles. The release studies show the encapsulated drugs in PLGA are released apparently by more than one release mechanism, while drugs released from liposomes apparently follow one stage mode of release. Nanoparticles similar to the ones prepared in this work have been studied to help interact with the BBB