Targeted Drug Delivery Across Blood-Brain-Barrier Using Cell Penetrating Peptides Tagged Nanoparticles

In the field of biomedical sciences, nanotechnology has emerged as a novel approach to design and develop drug delivery carriers (i.e. nanoparticles). The inspiration of nanoparticles as delivery vehicles for drugs or genes arose from the concept of viral mediated delivery. Researchers envied the enhanced transport efficiency of viruses but required a delivery method that did not incorporate the virus- induced pathological, immunological and oncological side-effects. Thus, bio-mimicked nanoparticles were prepared from synthetic polymers for efficient delivery of therapeutic molecules. However, biotherapeutics delivery across blood-brain-barrier is still a challenging task due to the inherent neuroprotective mechanism of the human brain. Recent studies suggest that cationic cell penetrating peptides can be used in designing targeted nanoparticles. This review describes the anatomical and physiological barriers of the brain with their special features and limitations for drug delivery and role of cationic cell penetrating peptides in designing nanoparticles for targeted biotherapeutics delivery to the brain. It emphasises the use of polymeric nanoparticles and their characteristics with respect to size, surface tolerability and multifunctionality. These properties aid them to cross the biological barriers of the brain. The multifunctionality of nanoparticles has been further explored with the application of cell penetrating peptides conjugated with nanoparticles for delivery at specialized location. The utilization of peptides on nanoparticles has encouraged and facilitated the approach of using non-invasive techniques not only to deliver drugs but also genes and proteins with minimal side-effects and toxicity when compared to conventional invasive techniques of therapeutic delivery to the brain. This technology has shown to be promising as a possible treatment method for a number of neurological disorders in both in vitro and in vivo models. Keywords: Polymeric nanoparticles, blood-brain barrier, cell penetrating peptides, multifunctionality, targeted delivery, nanocapsules, nanomedicine, nanotechnology, viral mediated delivery, cationic cell penetrating peptides, Central nervous system, blood, –, cerebrospinal fluid barrier, catalytic pockets of the enzyme/protein involved in the molecular mechanism of the d, nanocarriers, polyethylene glycol, brain endo-thelial cells, pericytes (PCs), homeostasis, zonulae occludens, Efflux Transporters, efflux pump, chemical drug delivery systems, epidural (EPI) delivery of multivesicular liposomes DepoFoam drug, Intracerebro Ventricular Delivery, Intracerebral Delivery, brain parenchyma, Convection Enhanced Delivery, Intravascular Delivery, Olfactory Pathway, nasal drug delivery, inflam-mogenicity, fibrogenicity, Transactivating Transcriptional Activator (TAT) Peptide, protein transductions, TAT-mediated transduction, intracellular delivery, cargoes, antennapedia homeodomain, dro-sophila, Transportan Peptide, Polyarginine Peptide, Adsorptive Mediated Transport, proteoglycans, lipid bilayer, Carrier Mediated Transport, transcytosis, Receptor Mediated Transport, transferrin receptor