Home Pharmacology Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs
Pharmacology JoVE (Open Access) Citable · DOI

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

DOI: 10.3791/2460-v
What you'll learn
  • Manufacture nanoformulated antiretroviral particles using wet milling, homogenization, and sonication
  • Assess macrophage uptake, retention, and sustained drug release from nanoART
  • Characterize nanoparticle morphology and size distribution by electron microscopy
  • Evaluate macrophage-based drug delivery potential for clinical HIV therapy
Protocol

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.

Difficulty
advanced
Total time
~3–5 days (manufacturing ~1–2 days; macrophage culture and uptake studies ~2–3 days)
Model organism
Human monocyte-derived macrophages (primary culture or THP-1 cells)
Biosafety
BSL-2

Steps

1
Manufacture nanoparticles by wet milling

Use NETZSCH MicroCer wet milling equipment to reduce bulk antiretroviral drug crystals (indinavir, ritonavir, efavirenz, atazanavir) to nanoparticle size.

▶ 03:21
2
Further reduce nanoART size by homogenization

Apply Avestin EmulsiFlex C5 homogenizer to milled nanoART suspensions to achieve uniform particle distribution and reduced mean diameter.

▶ 06:44
3
Optimize nanoparticle suspension by sonication

Use Cole Parmer ultrasonic processor to disperse and stabilize nanoART formulations, preventing aggregation.

▶ 07:52
4
Visualize and characterize nanoART morphology

Perform transmission electron microscopy and light scattering analysis to determine particle size, distribution, and morphology of final nanoformulations.

▶ 09:58
5
Culture macrophages and assess nanoART uptake

Differentiate monocytes to macrophages, expose to nanoART formulations, and measure intracellular drug uptake, retention kinetics, and sustained-release profiles.

▶ 10:56
6
Analyze and present representative results

Summarize nanoparticle characterization data, macrophage uptake/retention curves, and evidence supporting clinical potential of nanoART delivery.

▶ 15:37
💬 Comments coming soon