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Multifunctional Nanotherapeutics for the Treatment of neuroAIDS in Drug Abusers.

ABSTRACT: 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.

SUBMITTER: Jayant RD

PROVIDER: S-EPMC6113246 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Multifunctional Nanotherapeutics for the Treatment of neuroAIDS in Drug Abusers.

Jayant Rahul Dev RD Tiwari Sneham S Atluri Venkata V Kaushik Ajeet A Tomitaka Asahi A Yndart Adriana A Colon-Perez Luis L Febo Marcelo M Nair Madhavan M

Scientific reports 20180828 1

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 over ...[more]

PMID: 30154522

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Project description:Alzheimer's disease (AD) is the most prevalent form of dementia. It affects more than 30 million people worldwide and costs over US$ 1.3 trillion annually. AD is characterized by the brain accumulation of amyloid β peptide in fibrillar structures and the accumulation of hyperphosphorylated tau aggregates in neurons, both leading to toxicity and neuronal death. At present, there are only seven drugs approved for the treatment of AD, of which only two can slow down cognitive decline. Moreover, their use is only recommended for the early stages of AD, meaning that the major portion of AD patients still have no disease-modifying treatment options. Therefore, there is an urgent need to develop efficient therapies for AD. In this context, nanobiomaterials, and dendrimers in particular, offer the possibility of developing multifunctional and multitargeted therapies. Due to their intrinsic characteristics, dendrimers are first-in-class macromolecules for drug delivery. They have a globular, well-defined, and hyperbranched structure, controllable nanosize and multivalency, which allows them to act as efficient and versatile nanocarriers of different therapeutic molecules. In addition, different types of dendrimers display antioxidant, anti-inflammatory, anti-bacterial, anti-viral, anti-prion, and most importantly for the AD field, anti-amyloidogenic properties. Therefore, dendrimers can not only be excellent nanocarriers, but also be used as drugs per se. Here, the outstanding properties of dendrimers and derivatives that make them excellent AD nanotherapeutics are reviewed and critically discussed. The biological properties of several dendritic structures (dendrimers, derivatives, and dendrimer-like polymers) that enable them to be used as drugs for AD treatment will be pointed out and the chemical and structural characteristics behind those properties will be analysed. The reported use of these nanomaterials as nanocarriers in AD preclinical research is also presented. Finally, future perspectives and challenges that need to be overcome to make their use in the clinic a reality are discussed.

Project description:Introduction: Relapse is very common in drug abusers and contributes to a series of negative consequences. Effective addiction treatment exists but there are some problems in the implementation process. Mobile health (mHealth) offers a potential solution to improving recovery outcome for drug abusers in the community. The research team developed a community-based addiction rehabilitation electronic system (CAREs). The primary aim of this study is to explore whether the integrated rehabilitation based on program CAREs promotes drug abusers to keep abstinence. The secondary aim is to evaluate the impact of CAREs on interaction between drug users and service providers, and on addiction-related physical and social functions. Method and analysis: A randomized controlled trial (RCT) will be conducted. The study is a superiority trial with parallel group design. Seventy drug abusers who are newly ordered to undergo community rehabilitation will be recruited from the community in Shanghai. Participants will be 1:1 randomly assigned to receive integrated community rehabilitation by using CAREs or only receiving routine community rehabilitation for 6 months. Corresponding social workers will provide service and monitor their drug use behavior in accordance with the routine work-flow. Outcomes will be assessed at baseline and in the 6th month. The primary outcome is the performance on illicit drug urine test which will be carried out regularly twice per week during the study period. Secondary study outcomes include longest duration of sustained abstinence, days that participants interact with social workers, and the decrease rate of addiction-related issues severity index. Chi-square tests and ANOVAs will be used to compare characteristics of the members of the two groups. GEE will be used to compare the seven dimensions scores of the ASI between groups. Discussion: The study provides evidence for the feasibility and effectiveness of the "CAREs" system through comparing the results of the intervention group with the control group. This paper describes the design and methodology of the study. Ethics and dissemination: The Ethical Board of SMHC approved the study protocol. All participants will present for the informed consent process. After study completion, the results will be published. Trial Registration: ClinicalTrials.gov NCT03451344, https://clinicaltrials.gov/ct2/show/NCT03451344.

Dataset Information

Multifunctional Nanotherapeutics for the Treatment of neuroAIDS in Drug Abusers.

Publications

Multifunctional Nanotherapeutics for the Treatment of neuroAIDS in Drug Abusers.

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