TY - JOUR
T1 - Multifunctional Nanotherapeutics for the Treatment of neuroAIDS in Drug Abusers
AU - Jayant, Rahul Dev
AU - Tiwari, Sneham
AU - Atluri, Venkata
AU - Kaushik, Ajeet
AU - Tomitaka, Asahi
AU - Yndart, Adriana
AU - Colon-Perez, Luis
AU - Febo, Marcelo
AU - Nair, Madhavan
N1 - Funding Information:
We acknowledge financial support from NIH grants R01DA042706, R01DA037838; and R01DA040537 for MN and The Campbell Foundation Pilot Funding (Grant no: 800008886) for RDJ. We would also like to acknowledge NIH-AIDS Research Program for the ARV drugs, HIV-1 virus stock and NIDA for Meth stock. We would also like to acknowledge Dr. Marisela Agudelo lab (FIU) for the use of single cell flow cytometer facility and AMERI (FIU) for TEM imaging and other characterization instrumentation.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - HIV and substance abuse plays an important role in infection and disease progression. Further, the presence of persistent viral CNS reservoirs makes the complete eradication difficult. Thus, neutralizing the drug of abuse effect on HIV-1 infectivity and elimination of latently infected cells is a priority. The development of a multi-component [antiretroviral drugs (ARV), latency reactivating agents (LRA) and drug abuse antagonist (AT)] sustained release nanoformulation targeting the CNS can overcome the issues of HIV-1 cure and will help in improving the drug adherence. The novel magneto-liposomal nanoformulation (NF) was developed to load different types of drugs (LRAs, ARVs, and Meth AT) and evaluated for in-vitro and in-vivo BBB transmigration and antiviral efficacy in primary CNS cells. We established the HIV-1 latency model using human astrocyte cells (HA) and optimized the dose of LRA for latency reversal, Meth AT in in-vitro cell culture system. Further, PEGylated magneto-liposomal NF was developed, characterized for size, shape, drug loading and BBB transport in-vitro. Results showed that drug released in a sustained manner up to 10 days and able to reduce the HIV-1 infectivity up to ~40–50% (>200 pg/mL to <100 pg/mL) continuously using single NF treatment ± Meth treatment in-vitro. The magnetic treatment (0.8 T) was able to transport (15.8% ± 5.5%) NF effectively without inducing any toxic effects due to NF presence in the brain. Thus, our approach and result showed a way to eradicate HIV-1 reservoirs from the CNS and possibility to improve the therapeutic adherence to drugs in drug abusing (Meth) population. In conclusion, the developed NF can provide a better approach for the HIV-1 cure and a foundation for future HIV-1 purging strategies from the CNS using nanotechnology platform.
AB - HIV and substance abuse plays an important role in infection and disease progression. Further, the presence of persistent viral CNS reservoirs makes the complete eradication difficult. Thus, neutralizing the drug of abuse effect on HIV-1 infectivity and elimination of latently infected cells is a priority. The development of a multi-component [antiretroviral drugs (ARV), latency reactivating agents (LRA) and drug abuse antagonist (AT)] sustained release nanoformulation targeting the CNS can overcome the issues of HIV-1 cure and will help in improving the drug adherence. The novel magneto-liposomal nanoformulation (NF) was developed to load different types of drugs (LRAs, ARVs, and Meth AT) and evaluated for in-vitro and in-vivo BBB transmigration and antiviral efficacy in primary CNS cells. We established the HIV-1 latency model using human astrocyte cells (HA) and optimized the dose of LRA for latency reversal, Meth AT in in-vitro cell culture system. Further, PEGylated magneto-liposomal NF was developed, characterized for size, shape, drug loading and BBB transport in-vitro. Results showed that drug released in a sustained manner up to 10 days and able to reduce the HIV-1 infectivity up to ~40–50% (>200 pg/mL to <100 pg/mL) continuously using single NF treatment ± Meth treatment in-vitro. The magnetic treatment (0.8 T) was able to transport (15.8% ± 5.5%) NF effectively without inducing any toxic effects due to NF presence in the brain. Thus, our approach and result showed a way to eradicate HIV-1 reservoirs from the CNS and possibility to improve the therapeutic adherence to drugs in drug abusing (Meth) population. In conclusion, the developed NF can provide a better approach for the HIV-1 cure and a foundation for future HIV-1 purging strategies from the CNS using nanotechnology platform.
UR - http://www.scopus.com/inward/record.url?scp=85052517913&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-31285-w
DO - 10.1038/s41598-018-31285-w
M3 - Article
C2 - 30154522
AN - SCOPUS:85052517913
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12991
ER -