A comprehensive analysis of the evolution of brain drug delivery is presented, starting from the initial discovery in 1914 that the blood-brain barrier (BBB) prevented the entry of a syphilis drug called salvarsan into the brain. This barrier has posed challenges in delivering drugs to the central nervous system (CNS), resulting in the predominance of lipid-soluble small molecules among FDA-approved CNS drugs. However, there is potential to modify drugs that cannot cross the BBB to utilize the endogenous carrier-mediated transport system of the BBB. This review critically examines the advantages and limitations of various brain drug delivery technologies. Acyclovir (ACV), a guanine derivative antiviral drug, has been on the market for a long time and is available in various forms for oral, topical, and parenteral administration. Despite being an old molecule, it still holds its ground against newer antiviral agents due to its superior clinical application, which includes the ability to suppress recurrence, minimal drug interactions, and affordability. Although ACV is slightly water-soluble, less permeable, and poorly bioavailable, it has the potential to be an effective antiviral molecule. Over the past decade, more than 100 research works have been conducted to explore physicochemical modifications and novel dosage forms to enhance its potentia.
The delivery of drugs to the central nervous system (CNS) is crucial for effectively managing viral infections. However, the presence of natural barrier structures, such as the blood-brain barrier, poses a significant challenge in allowing anti-HIV compounds to reach this anatomical site. Nanotechnology-based strategies offer promising solutions for enhancing drug delivery to the CNS. These approaches have the potential to extend the circulation of drugs in the body, facilitate their passage across the blood-brain barrier, reduce their removal from the CNS, and enable targeted delivery to specific cells and tissues within the CNS. Additionally, nanotechnology can also facilitate intracellular drug delivery, further enhancing the efficacy of antiviral treatments