Yadollah Omidi1, Jaleh Barar. 1. Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract
INTRODUCTION: Entry of blood circulating agents into the brain is highly selectively con-trolled by specific transport machineries at the blood brain barrier (BBB), whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. METHODS: Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. RESULTS: Brain capillary endothelial cells (BCECs) form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics). CONCLUSION: The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent.
INTRODUCTION: Entry of blood circulating agents into the brain is highly selectively con-trolled by specific transport machineries at the blood brain barrier (BBB), whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. METHODS: Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. RESULTS: Brain capillary endothelial cells (BCECs) form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics). CONCLUSION: The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent.
Entities:
Keywords:
Blood-Brain Barrier; Brain Capillary Endothelial Cells; Brain Tumor; Drug Delivery; Drug Targeting; Nanomedicines,Theranostics
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