REVIEW ARTICLE ON: BRAIN-TARGETED DRUG DELIVERY VIA CHEMICAL MODIFICATIONS: STRATEGIES AND RECENT ADVANCES

Prof. Dev Prakash Dahiya, *Palak Kumari, Anchal Sankhyan, Manjula Verma, Samriti Naik

ABSTRACT

Central nervous system (CNS) disorders such as Parkinson’s disease, Alzheimer’s disease, epilepsy, and brain tumors remain among the most challenging to treat due to the restricted access of drugs to the brain. The main barrier is the blood-brain barrier (BBB), a complex physiological interface that tightly regulates the entry of substances into the brain parenchyma. Most therapeutic molecules are unable to cross this barrier in adequate concentrations, significantly limiting the effectiveness of treatment. Among the various strategies to overcome this challenge, chemical modification of drug molecules has emerged as a promising approach to enhance brain permeability. These modifications aim to improve physicochemical characteristics, mimic endogenous substrates of brain transporters, or utilize receptor-mediated mechanisms. Techniques such as prodrug design, lipidization, receptor- and transporter-ligand conjugation, and bioisosteric substitutions have demonstrated improved brain uptake in both experimental and clinical settings. This review provides a detailed overview of these strategies, highlighting the design rationale, recent case studies, practical challenges, and future directions in chemically engineered CNS drug delivery.

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