Volume : 13, Issue : 08, August – 2026
Title:
BEYOND THE BLOOD–BRAIN BARRIER: MEDICINAL CHEMISTRY STRATEGIES FOR BRAIN-TARGETED PRODRUG DESIGN
Authors :
Omkar Rai*, Soma Sekhar Pulamarasetti, Rupesh Soni, Soumik Das
Abstract :
The blood–brain barrier (BBB) is a highly selective neurovascular interface that protects the central nervous system (CNS), but also limits therapeutic access to the brain. In medicinal chemistry, the prodrug design provides a reversible approach to change polarity, ionization, lipophilicity, transporter recognition and metabolic stability to allow delivery of a pharmacologically active parent drug to the CNS and its regeneration upon crossing the barrier. This extended review deals with the chemical rationale of brain-directed prodrugs, emphasizing passive-diffusion enhancement, masking of ionizable groups, transporter-mediated uptake, receptor-mediated delivery, redox chemical delivery systems, intracellular trapping and self-immolative or cascade activation. The roles of P-glycoprotein and associated efflux systems, disease-state alterations in the BBB, in vitro and in vivo evaluation, quantitative pharmacokinetics/pharmacodynamics and computational approaches are also reviewed. Comparative tables summarize design variables, representative historical and contemporary strategies, activation mechanisms, experimental models and translational risks. Original schematic figures and literature-mapping charts are provided to make the structure property-mechanism relationships visually explicit. The primary takeaway is that BBB penetration alone is not enough to define successful brain targeting. The prodrug must remain sufficiently stable in systemic compartments, cross the relevant brain barrier, undergo productive activation in the intended tissue or cell type, and generate adequate free parent-drug exposure while minimizing peripheral toxicity. Recent literature reinforces a shift from generic lipophilicity enhancement toward mechanism-based, multi-parameter and site-selective prodrug engineering.
Keywords: Blood–brain barrier; CNS drug delivery; brain-targeted prodrug; medicinal chemistry; LAT1; GLUT1; transporter-mediated delivery; efflux transporters; chemical delivery system; redox targeting; bioactivation; self-immolative linker; neuropharmacology; PK/PD; CNS drug discovery.
Cite This Article:
Please cite this article in press Omkar Rai et al., Beyond the Blood–Brain Barrier: Medicinal Chemistry Strategies for Brain-Targeted Prodrug Design. Indo Am. J. P. Sci, 2026; 13(08).
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Volume : 13, Issue : 08, August – 2026
Title:
EVALUATION OF ANTIHYPERLIPIDEMIC ACTIVITY OF SAPINDUS EMARGINATUS IN RATS
Authors :
Chinthala Jamima*, Dr.R.narasimha Rao, Dr.N. Raghunandhan
Abstract :
Obesity and hyperlipidemia have become major disorders predominantly causing prevailing cardiovascular diseases and ultimately death. The prolonged use of anti-obesity drugs and statins for reducing obesity and blood lipid levels is leading toward adverse effects of kidneys and muscles, specifically rhabdomyolysis. The objective of this study is to evaluate potential of seeds of Sapindus emarginatus against hyperlipidemia. In this model of Hyperlipidemia, 30 adult male wistar rats (200-250gms) were evenly divided into 5 groups in both groups. Group-1 and Group-2 served as untreated and model controls respectively, while Group-3, 4 and 5 were the treatments groups which were simultaneously treated with standard, 100 and 200 mg/kg extract respectively along with High Fat Diet. On last day, blood samples for biochemical parameters, were obtained under inhaled diether anaesthesia. The outcomes of this study were expressed as mean standard error and data were evaluated by using analysis of variance followed by multiple comparisons. Oral administration of 100 mg/ kg and 200mg/kg body weight of Methanolic extract residual fraction of Moringa oleifera. Leaves exhibited a significant reduction (P < 0.01) in serum lipid parameters such as triglycerides, total cholesterol, low density lipoprotein (LDL), very LDL and increase in high density lipoprotein in hyperlipidemic rats when compared with hyperlipidemic control in both models. Our results demonstrated that Methanolic extract fraction of Sesbania grandiflora. Possessed significant antihyperlipidemic activity.
Keywords: Sesbania grandiflora, Cholesterol, LDL, triglycerides and antihyperlipidemic activity.
Cite This Article:
Please cite this article in press Chinthala Jamimaet al., Evaluation of Antihyperlipidemic activity of Sapindus Emarginatus in rats,, Indo Am. J. P. Sci, 2026; 13(08).
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