Characterization of Nanodiamond-based anti-HIV drug Delivery to the Brain

Upal Roy,Xiaohua Liu,Paul Barber,Surendra Saxena,Andriy Durygin,Venkata Atluri,Vadym Drozd,Thomas G Voss,Jesse Rodriguez,Madhavan Nair

doi:10.1038/s41598-017-16703-9

Abstract

Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the ineffective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature–making it a more efficient drug carrier than other carbon-based materials. Considering its potential and importance, we have characterized unmodified and surface-modified (-COOH and -NH2) nanodiamond for its capacity to load the anti-HIV-1 drug efavirenz and cytotoxicity, in vitro. Overall, our study has established that unmodified nanodiamond conjugated drug formulation has significantly higher drug loading capacity than surface-modified nanodiamond with minimum toxicity. Further, this nanodrug formulation was characterized by its drug dissolution profile, transmigration through the BBB, and its therapeutic efficacy. The present biological characterizations provide a foundation for further study of in-vivo pharmacokinetics and pharmacodynamics of nanodiamond-based anti-HIV drugs.

Highlights

Human Immunodeficiency Virus Type 1 (HIV-1) infection remains one of the leading causes of mortality in the world
Among the many nanocarbon materials that have been investigated for use as drug carriers, ND, is the most promising due to its many favorable properties, including, chemical inertness, biocompatibility, and easy availability compared to other nanocarbon materials[17]
Reactive Oxygen Species (ROS) study explained that ND-COOH can induce more ROS production than ND or ND-NH2

Summary

Introduction

HIV-1 infection remains one of the leading causes of mortality in the world. the development of combination antiretroviral therapy (cART) has significantly improved the mean lifespan of HIV-1 infected patients, the virus persists inside reservoir organs, such as the CNS and lymphoid tissues1,2. cART dosing regimens show limitations based on distribution, metabolism, drug stability, and limited penetration into the CNS. Previous studies have demonstrated its capability as a drug carrier of doxorubicin, purvalanol A, 4-hydroxytamoxifen, and dexamethasone for human colon cancer, liver cancer, breast cancer and blood cancer therapies, respectively These studies indicated that ND possesses major cancer drug loading and sustained release capacities without producing any inflammatory reaction in human cells[18,19,20,21,22]. ND has distinct advantages compared to other carbon-based nanomaterials, such as carbon nanotubes and nanographene, which have shown toxicity in many other studies They are not dispersed in water, which makes it difficult to use these excipients in nanoformulations[23,24,25]. By applying ND towards drug delivery to treat HIV-1 CNS reservoirs, we have established that the conjugation of EFV with functionalized ND will substantially increase its therapeutic efficacy

Objectives

Methods

Results

Conclusion