A Sublingual Drug Delivery System for the Treatment of Depression

Abstract

Depression is a common mental illness that has affected many individuals globally. Several antidepressant drugs have been developed over the years, and the primary method of drug administration is the oral route. The challenge with orally administered antidepressants is the bioavailability of the drug in the systemic circulation or its site of action. Only a fraction of the drug is available at the target site due to first-pass metabolism in the liver and digestive system. Another limitation that affects the drug delivery of an antidepressant is the presence of the blood- brain barrier (BBB). The ability of these drugs to achieve optimal therapeutic levels in the central nervous system (CNS) lies in their ability to effectively cross the BBB. To overcome these limitations, various innovative drug delivery systems have been developed. Nanoparticles have been explored as potential drug delivery systems (DDS) having shown the ability to encapsulate drugs and enhance drug delivery to the brain. Different types of nanoparticles, such as polymeric or liposome nanoparticles, can be designed to have particular drug release profiles, improving the efficacy of the drug and reducing side effects of therapy. The current study will assess the potential of poly (lactic-co-glycolic acid) as a drug delivery system for the sublingual delivery of amitriptyline for the treatment of depression. It will cover the statistics and impact of depression along with the currently available treatment options and their limitations such as low bioavailability and first-pass metabolism, to name a few. Furthermore, drug delivery methods that have been considered in previous studies, the use of alternative routes, drug delivery systems used to improve antidepressant therapy, the challenges with conventional drug therapy, the role of the blood-brain barrier, and alternative drug delivery methods currently available in an effort to improve conventional drug delivery systems for depression were discussed. The primary goal of the study was to synthesize a Amitriptyline loaded poly (lactic-co-glycolic acid) (PLGA) nanosuspension for sublingual delivery to the brain. Based on literature, PLGA enhances drug delivery to specific cells or tissues and improves the efficacy of the drug. A Amitriptyline loaded PLGA nanosuspension were formulated by nanoprecipitation. Fourier-transform infrared spectroscopy (FTIR), Zetasizer, and Differential Scanning Calorimetry (DSC) were used to determine the physiochemical properties of the nanosuspension. The synthesised nanoparticles were 137.7nm in size, with polydispersity index (PDI) of 0,064 and a zeta potential of -8.98. High Performance Liquid Chromatography (HPLC) was used to determine the drug release content of the nanosuspension at differing time intervals. The drug release profile of amitriptyline exhibited a burst release of approximately 60% in the first hour, followed by a gradual release up to approximately 68% within 8 hours. The high drug release profile of the nanosuspension and the 5 ability of the biomaterials to cross the BBB makes this drug delivery system a desirable system compared to the conventional tablet-based delivery systems.