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

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.

<p>Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation</p>

“…In addition, alternate routes of drug delivery are proposed. 4 The intranasal route is one of the alternative options and is considered a noninvasive route with various advantages and an enhanced efficiency. The olfactory epithelium of the CNS provides direct contact with the external environment and so direct nose-to-brain delivery is the hallmark feature of the intranasal route.…”

“…Thus, mucoadhesive and thermosensitive formulations are considered ideal for administration by the intranasal route. 4,9 Saquinavir mesylate (SQ) is an antiviral agent acting by the mechanism of protease inhibition. SQ has low water solubility and shows poor permeation into the brain.…”

Functionalization of Carbon Nanomaterials for Biomedical Applications

“…The NDs special biocompatibility and safety can be coupled to the rich chemistry provided by the diamond surface [287] which enables the grafting of a wide variety of molecules [288,289]. This renders diamond an extraordinary platform useful for different kinds of applications [284,290] spanning from quantum sensing [291,292], to fluorescent probes and tracking [293,294], bioimaging [295,296], drug delivery [297,298] and nano-biomedicine [299,300].…”

Hemocompatibility of Carbon Nanostructures

“…Thanks to their surface chemistry, most CNs can be easily conjugated with various functional groups and chemical moieties in an attempt to improve some features that are critical in the biological environment (e.g., colloidal dispersibility and stability), to address the desired biological response or to reach specific target organs. Various active molecules, including chemotherapeutics, antiretroviral, antibacterial, and anti-inflammatory compounds [18][19][20], have been conjugated to CNs with high drug loading efficiency.…”