Therapeutical Neurotargeting via Magnetic Nanocarrier: Implications to Opiate-Induced Neuropathogenesis and NeuroAIDS.
Magnetite (Fe3O4) is the most commonly and extensively explored magnetic nanoparticles (MNPs) for drug-targeting and imaging in the field of biomedicine. Nevertheless, its potential application as safe and effective drug-carrier for CNS (Central Nervous System) anomalies is very limited. Previous studies have shown an entangled epidemic of opioid use and HIV infection and increased neuropathogenesis. Opiate such as morphine, heroine, etc. are used frequently as recreational drugs. Existing treatments to alleviate the action of opioid are less effective at CNS level due to impermeability of therapeutic molecules across brain barriers. Thus, development of an advanced nanomedicine based approach may pave the way for better treatment strategies. We herein report magnetic nanoformulation of a highly selective and potent morphine antagonist, CTOP (D-Pen-Cys-Tyr-DTrp-Orn-Thr-Pen-Thr-NH2), which is impenetrable to the brain. MNPs, synthesized in size range from 25 to 40 nm, were characterized by Transmission electron microscopy and assembly of MNPs-CTOP nanoformulations were confirmed by FTIR spectroscopy and fluorescent detection. Flow-cytometry analysis showed that biological efficacy of this nanoformulation in prevention of morphine induced apoptosis in peripheral blood mononuclear cells remains equivalent to that of free CTOP. Similarly, confocal microscopy reveals comparable efficacy of free and MNPs bound CTOP in protecting modulation of neuronal dendrite and spine morphology during morphine exposure and morphine-treated HIV infection. Further, typical transmigration assay showed increased translocation of MNPs across in vitro blood-brain barrier upon exposure of external magnetic force where barrier integrity remains unaltered. Thus, the developed nanoformulation could be effective in targeting brain by application of external magnetic force to treat morphine addiction in HIV patients.
Vidya
V
Sagar
Sudheesh
S
Pilakka-Kanthikeel
Venkata S R
VS
Atluri
Hong
H
Ding
Adriana Y
AY
Arias
Rahul D
RD
Jayant
Ajeet
A
Kaushik
Madhavan
M
Nair
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004058:Diffusion; D004347:Drug Interactions; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008422:Materials Testing; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D053610:Opiate Alkaloids / Q000506:poisoning*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D016896:Treatment Outcome
D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D053610:Opiate Alkaloids; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin