Development and characterization of a novel nanoparticle for delivery of siRNA as a potential strategy for treatment of HIV infection in the brain
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Human immunodeficiency virus (HIV) infection and subsequent invasion of the central nervous system (CNS) can lead to the development of neurocognitive disorders such as HIV associated dementia. The presence of the blood-brain barrier (BBB) and its restrictive nature has made traditional therapeutics largely unsuccessful, allowing HIV a key sanctuary site for continued infection. Nanomedicine, in particular nanoparticles for drug delivery, is an emerging field looking to overcome the hurdles of effective drug delivery. Chitosan nanoparticles in particular have gained much interest due to their ability to form stable complexes with small interfering RNA (siRNA), short doublestranded nucleic acids capable of silencing gene expression in cells. The present work aims to develop a chitosan nanoparticle formulation for delivery of siRNA and subsequent gene knockdown to inhibit replication of HIV in brain cells. In the current study, we have successfully fabricated nanoparticles of suitable size with high siRNA encapsulation efficiency. The nanoparticles also demonstrated increased cellular uptake compared to commercially available transfection reagent with no detrimental effects on cell viability. As work continues on gene knockdown, cell targeting, and drug release studies, early results are promising in hopes of developing an effective method for inhibition of HIV replication in brain cells.