title: Targeted brain derived neurotropic factors (BDNF) delivery across the blood-brain barrier for neuro-protection using magnetic nano carriers: an in-vitro study.
abstract: Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effective in-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.
authors: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.
authors: Sudheesh
authors: S
authors: Pilakka-Kanthikeel
authors: Venkata Subba Rao
authors: VS
authors: Atluri
authors: Vidya
authors: V
authors: Sagar
authors: Shailendra K
authors: SK
authors: Saxena
authors: Madhavan
authors: M
authors: Nair
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002452:Cell Count; D049229:Dendritic Spines / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008954:Models, Biological; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D061251:Primary Cell Culture
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D018696:Neuroprotective Agents; D009020:Morphine
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