Microemulsions and Nanoemulsions for Targeted Drug Delivery to the Brain

Rajshree      L. Shinde; Anil      B. Jindal; Padma      V. Devarajan

Abstract

Brain disorders including neurological disorders, inflammatory and infectious conditions of brain, brain cancer and brain stroke pose a significant challenge globally. The blood brain barrier (BBB) an important physiological barrier limits access of drug to the site of action. While passive diffusion and endogenous carrier mediated transport are two important mechanisms for the transport of substances across the BBB into the luminal side, efflux transporters severely limit drug concentration. Drug delivery strategies must address on one hand methods to bypass the BBB and on the other hand methods to overcome efflux transporters. Lipid based nanocarriers, liposomes and solid lipid nanoparticles are widely investigated for brain targeting. Emulsion based lipid nanocarriers like microemulsions (ME) and nanoemulsions (NE) provide an additional advantage of greater bypass of the reticulo-endothelial system with improved brain targeting. More recently the promise of ME and NE for brain delivery has been cited. Oil, surfactants and water are the primary components of ME and NE. ME may additionally comprise cosurfactants. The reviews discusses the development of ME/NE, design of functional ME/NE by appropriate selection of primary ME/NE components which could provide improved brain delivery by functioning as stealth agent, absorption enhancer, efflux transporter inhibitor or even facilitate receptor mediated endocytosis. Engineering functional ME/NE into multifunctional ME/NE as a strategy to further enhance brain targeting is also presented. Functional and multifunctional excipients have been discussed. The possible routes of delivery namely intravenous, oral and intranasal and therapeutic applications of ME/NE designed for brain targeting is also reviewed.

Keywords: Microemulsion, Brain targeting, Blood Brain Barrier, Nose to brain delivery, neurological disorders, brain cancer, brain stroke, efflux transporters, liposomes, Nanoemulsion, polymeric nanoparticles, occludin, claudins, junctional adhesion molecule, endothelial cells, luminal, abluminal, Passive Diffusion, lipophilicity, Endogenous Carrier-Mediated Transport, Carrier-mediated Facilitated Transport, organic cation transport, organic anion transporters, exocytosis, P-Glycoprotein, Breast Cancer Resistance Protein, daunorubicin, doxorubicin, topotecan, sodium, daunomycin, amphotericin, demonstrated, tobramycin, idarubicin, camptothecin