Nanotechnology approaches for delivery of cytochrome P450 substrates in HIV treatment

ABSTRACT

Introduction: Antiretroviral therapy (ART) has led to a significant reduction in HIV-1 morbidity and mortality. Many antiretroviral drugs (ARVs) are metabolized by cytochrome P450 (CYP) pathway, and the majority of these drugs are also either CYP inhibitors or inducers and few possess both activities. These CYP substrates, when used for HIV treatment in the conventional dosage form, have limitations such as low systemic bioavailability, potential drug–drug interactions, and short half-lives. Thus, an alternative mode of delivery is needed in contrast to conventional ARVs.

Areas covered: In this review, we summarized the limitations of conventional ARVs in HIV treatment, especially for ARVs which are CYP substrates. We also discussed the preclinical and clinical studies using the nanotechnology strategy to overcome the limitations of these CYP substrates. The preclinical studies and clinical studies published from 2000 to February 2019 were discussed.

Expert opinion: Since preclinical and clinical studies for prevention and treatment of HIV using nanotechnology approaches have shown considerable promise in recent years, nanotechnology could become an alternative strategy for daily oral therapy as a future treatment.

Trial registration: ClinicalTrials.gov identifier: NCT02631473.

Trial registration: ClinicalTrials.gov identifier: NCT02165202.

Trial registration: ClinicalTrials.gov identifier: NCT02547870.

Trial registration: ClinicalTrials.gov identifier: NCT02076178.

KEYWORDS:

• Antiretroviral drugs
• CYP substrates
• HIV
• nanotechnology

Article highlights

• Most of the antiretroviral drugs (ARVs) are metabolized by cytochrome P450 (CYP) pathway and the majority of these drugs are also either CYP inhibitors or inducers, and few possess both activities.

• These CYP substrates, inhibitors, and inducers, when used for HIV treatment in conventional dosage forms, have limitations including low systemic bioavailability, potential drug–drug interactions, and short half-lives. Thus, current ARVs require either pharmacological boosting or regular daily dosing.

• Nanoformulation can be designed based on the need to show the controlled release profile, high permeability, biodegradation, or targeting capability. Although only a few of nanoformulations have reached the clinical trials for HIV treatment, nanotechnology may provide a new approach for safe and efficient delivery of ARVs for long-term therapy.

• We reviewed the most commonly used nanoformulation of CYP substrates in HIV treatment including polymeric nanoparticles, solid lipid nanoparticles, and polymer micelles in this article.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors were supported by the grants AA022063, DA047178, and CA213232.