Formulation Design, Optimization, and Evaluation of Solid Lipid Nanoparticles Loaded With an Antiviral Drug Tenofovir...

Area of Science:

• Pharmaceutical Nanotechnology
• Drug Delivery Systems
• Antiviral Therapeutics

Background:

• Tenofovir (TNF), an essential antiretroviral medication for HIV treatment, suffers from poor oral bioavailability.
• Limitations include low permeability, susceptibility to gut metabolism, and P-glycoprotein (P-gp) efflux transport.
• Solid lipid nanoparticles (SLNs) represent an emerging lipid-based formulation strategy with potential to overcome these barriers.

Purpose of the Study:

• To formulate and optimize tenofovir (TNF)-loaded solid lipid nanoparticles (SLNs) for enhanced oral bioavailability.
• To investigate the critical quality attributes influencing SLN characteristics and drug release.
• To evaluate the in vitro, ex vivo, and in vivo performance of the optimized TNF-SLN formulation.

Main Methods:

• SLNs were prepared using the microemulsion method with Compritol 888 ATO.
• A Box-Behnken design optimized lipid/surfactant content and homogenization time, assessing particle size (PS) and entrapment efficiency.
• Characterization included PS, zeta potential (ZP), polydispersity index, in vitro release, ex vivo permeation, solid-state analysis (DSC, PXRD), SEM, and in vivo pharmacokinetic studies in rats.

Main Results:

• The optimized formulation (F10) exhibited a small particle size (449.90 nm), narrow distribution (0.304), high entrapment efficiency (83.13%), and negative ZP (-18.10 mV).
• In vitro release followed first-order kinetics, with 99% drug release over 24 hours.
• In vivo studies in rats demonstrated a 12.4-fold increase in tenofovir bioavailability compared to the pure drug solution.

Conclusions:

• Solid lipid nanoparticles (SLNs) effectively enhance the oral bioavailability of tenofovir (TNF).
• SLNs show significant potential in overcoming common drug delivery challenges like poor permeability and efflux transport.
• This formulation strategy offers a promising approach for improving the therapeutic efficacy of tenofovir and similar drugs.