Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

作者：Shantanu Balkundi*1, Ari S. Nowacek*1, Upal Roy1, Andrea Martinez-Skinner1, JoEllyn McMillan1, Howard E. Gendelman1 1Department of Pharmacology and Experimental Neuroscience,University of Nebraska Medical Center

简介：Nanoparticles of indinavir, ritonavir, efavirenz and atazanavir were manufactured using wet milling, homogenization and ultrasonication. These nanoformulations, collectively termed nanoformulated antiretroviral therapy (nanoART), assessed macrophage-based drug delivery. Monocyte-derived macrophage nanoART uptake, retention and sustained release were determined. These preliminary studies suggest the potential of nanoART for clinical use.

全文：

Overview

This study focuses on the manufacturing and testing of crystalline antiretroviral nanoparticles, termed nanoART, for enhanced drug delivery via macrophages. The research evaluates the uptake, retention, and sustained release of these nanoparticles in human monocyte-derived macrophages.

Key Study Components

Area of Science

Nanomedicine
Pharmacology
Antiretroviral therapy

Background

Antiretroviral drugs are crucial for treating HIV.
Nanoparticle formulations can improve drug delivery and efficacy.
Macrophages play a significant role in drug uptake and release.
Previous studies have shown potential benefits of nanoformulated therapies.

Purpose of Study

To manufacture and characterize antiretroviral nanoparticles.
To assess the cellular uptake and release mechanisms in macrophages.
To evaluate the in vitro antiretroviral efficacy of nanoART.

Methods Used

Wet milling, homogenization, and ultrasonication for nanoparticle production.
Isolation and culture of primary monocytes into macrophages.
Measurement of drug levels using high-performance liquid chromatography (HPLC).
Assessment of reverse transcriptase activity in infected cultures.

Main Results

Successful manufacturing of nanoART with desired physical properties.
Demonstrated facilitated uptake and sustained release in macrophages.
Robust antiretroviral efficacy observed in vitro.
Potential for improved bioavailability and reduced side effects.

Conclusions

NanoART shows promise for clinical applications in HIV treatment.
Further research is needed to optimize formulations and delivery methods.
This approach may enhance patient compliance and treatment outcomes.

Frequently Asked Questions

What is nanoART?

NanoART refers to nanoparticles formulated from antiretroviral drugs aimed at improving drug delivery and efficacy.

How are the nanoparticles manufactured?

They are manufactured using techniques like wet milling, homogenization, and ultrasonication.

What role do macrophages play in this study?

Macrophages are used to assess the uptake, retention, and release of the nanoparticles.

What methods are used to evaluate the efficacy of nanoART?

The efficacy is evaluated through measurements of drug levels and reverse transcriptase activity in infected cultures.

What are the potential benefits of using nanoART?

Potential benefits include improved bioavailability, reduced side effects, and enhanced patient compliance.

标签: Methods Development, Blood Borne, Macrophage, Nanoformulated Antiretroviral Drugs, Pharmacodynamics, Bioavailability, Drug Toxicities, Nanomedicine, ART Regimens, Compliance, Drug Pharmacokinetics, Manufacturing NanoART, Surfactant Lipid Coating, Wet Milling, High-pressure Homogenization, Polymer Suspension, Ultrasonication, Physical Properties, Particle Size, Charge, Shape, Biologic Properties, Cell Uptake, Retention, Cytotoxicity, Antiretroviral Efficacy, Human Monocyte-derived Macrophages (MDM), Peripheral Blood Monocytes Isolation, Leukopacks Purification,