Development of L-carnosine functionalized iron oxide nanoparticles loaded with dexamethasone for simultaneous therapeutic potential of blood brain barrier crossing and ischemic stroke treatment

Abstract

The development of suitable drug delivery carriers is significant in biomedical applications to improve the therapeutic efficiency. Recent progress in nanotechnological fields, paved the way for the formulation of variety of drug carriers. The brain disorders such as ischemic stroke, brain cancer, and CNS disorders were poorly treated due to the presence of blood brain barrier that hinders the passage of drugs to the brain. Hence, the formulated drugs should have the ability to cross the blood-brain barrier (BBB) for ischemic stroke treatment. In the present work, we have synthesized PLGA functionalized magnetic Fe3O4 nanoparticle (MNP) with L-carnosine peptide (LMNP) composite loaded with dexamethasone (dm@LMNP) and demonstrated as efficient drug delivery platform for simultaneous BBB crossing and treatment of ischemic stroke. The surface morphology, particles size and zeta potential of the prepared material was studied from SEM, PSD, PDI and TEM analyses. The drug loading of dexamethasone in LMNP (dm@LMNP) vesicles was found to be 95.6 ± 0.2%. The in vitro drug release kinetics displayed that prepared composited LMNP material provides controlled and sustainable releasing efficiency at pH 7.4 and 5.8 when compared to the PLGA NPs and free dexamethasone drug molecules. The cytotoxicity and the biocompatibility test results were found to be satisfactory. The L-carnosine loaded nano-formulation has been greatly leads to effective BBB crossing to access the brain tissues. These results showed that the Fe3O4 nanoparticles/PLGA polymer can be used as an effective drug carrier for the treatment of stroke and simultaneous blood brain barrier crossing.