Indinavir-Loaded Nanostructured Lipid Carriers to Brain Drug Delivery: Optimization, Characterization and Neuropharmacokinetic Evaluation

Curr Drug Deliv. 2019;16(4):341-354. doi: 10.2174/1567201816666190123124429.


Purpose: As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB).

Methods: To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a "one-factor-at-a-time" screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study.

Result: The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior.

Conclusion: As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.

Keywords: Blood-Brain Barrier (BBB); Highly Active Anti-Retroviral Therapy (HAART); Nanostructured Lipid Carriers (NLC); indinavir; neuropharmacokinetic analysis; transferrin..

MeSH terms

  • Animals
  • Anti-Retroviral Agents / chemistry
  • Anti-Retroviral Agents / pharmacokinetics*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Indinavir / chemistry
  • Indinavir / pharmacokinetics*
  • Lipids / chemistry*
  • Male
  • Nanostructures / chemistry*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacokinetics*
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Surface Properties
  • Transferrin / chemistry


  • Anti-Retroviral Agents
  • Drug Carriers
  • Lipids
  • Neuroprotective Agents
  • Transferrin
  • Indinavir