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Nucleic Acids-based Nanotherapeutics Crossing the Blood Brain Barrier

[ Vol. 17 , Issue. 2 ]

Author(s):

Noha Nafee and Noha Gouda   Pages 154 - 169 ( 16 )

Abstract:


The restless endeavors revealing the molecular pathways underlying many neurodegenerative diseases and brain tumors have paved the way for the introduction of the selective exogenous gene-based therapeutics. The implicated active biomolecules encompass mainly negatively-charged nucleic acids ranging from DNA, mRNA, non-coding RNAs (small-interfering RNA, siRNA, and microRNA, miRNA), to antisense oligonucleotides. They selectively interfere with the genes translational and/or transcriptional processes.

Although many reviews previously addressed brain targeting, a thorough correlation between the molecular properties of these biomacromolecules, the nature of blood brain barrier (BBB) in the accompanying pathological condition, the intracellular targets, as well as the design of the delivery system which will transport the bioactive cargo to the target cells attempting efficient delivery to the active sites in the brain will be appraised.

In this review, we will further discuss the tremendous advances in non-viral gene delivery nanosystems currently investigated (starting from self-assembled nanoplexes using cationic polymers or lipids and going through liposomes, aptamers, polymersomes, exosomes, dendrimers and nanoparticles). Unlike previous reviews on this topic, functionalization strategies of the nanocarriers promoting either surface receptor binding or intracellular targeting of the cranial cells will be highlighted, with special emphasis on tailoring smart nanomedicines according to the CNS disease condition. In addition, newly-developed evaluation approaches, cell culture models studying BBB permeability and manipulation of the barrier function of the brain via focused ultrasound will be addressed.

Keywords:

Nanocarriers, Brain delivery, Neurodegenerative diseases, Glioma, Brain transporters, Gene delivery, mRNA.

Affiliation:

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria



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