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Ane Nishitha Vijayan,Janani Indrakumar,Sankaranarayanan Gomathinayagam,Kodiveri Muthukaliannan Gothandam,Purna Sai Korrapati 한국고분자학회 2022 Macromolecular Research Vol.30 No.8
The blood-brain barrier (BBB) curtails the permeability of neuroprotective drugs to the brain thus restricting the effective delivery of therapeutics for neurodegenerative disorders. Recently, greater emphasis has been given for polymeric nanoparticles as a potential delivery system to transport drugs across the blood-brain barrier. This study focuses on the cellular route, localization and enhancement of uptake of drug loaded polymeric nanoparticles for delivery across the blood-brain barrier. We have optimized and synthesized polylactic-co-glycolic acid (PLGA) nanoparticles as a carrier for the delivery of drugs across the barrier. Cell penetrating peptide trans-activating transcriptor (TAT) was conjugated with the polymer through covalent bonding for increasing the efficiency of drug delivery across the BBB. Rhodamine-B was used as a model drug to study the release of drugs from the synthesized nanoparticle and finally the in vivo uptake in a mice model was checked. The size of the synthesized nanoparticles was in the nanometer range and the release profile revealed a rapid release appropriate for brain delivery. The cellular uptake experiments revealed that the peptide conjugated nanoparticle was readily taken up by the cells through macropinocytosis. Finally, to overcome the challenges for drugs to cross the BBB in an in vivo system, we have tracked the bioavailability of the nanoparticles in a mice model. Here we report an enhanced uptake of the peptide functionalized drug delivery carrier to successfully deliver and track therapeutic molecules across the blood-brain barrier in vivo.