Oral Delivery of Indinavir Using mPEG-PCL Nanoparticles: Preparation, Optimization, Cellular Uptake, Transport and Pharmacokinetic Evaluation

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2123-2133. doi: 10.1080/21691401.2019.1616553.

Abstract

Introduction: Indinavir (IDV) is a potent HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV). IDV is a weak base with limited aqueous solubility in its unprotonated form; therefore, solubility of IDV in the gastrointestinal tract fluids is the rate-limiting step of its absorption and onset of action. However, in many cases, drugs are not absorbed well in the gastrointestinal tract; polymer nanoparticles were recognized as an effective carrier system for drug encapsulation and are now studied as a vehicle for oral delivery of insoluble compounds. Preparation of methoxy poly (ethylene glycol)-poly (e-caprolactone) (mPEG-PCL) nanoparticles is among the strategies to overcome low bioavailability of drugs with poor aqueous solubility. Materials and method: The structure of the copolymers was characterized using 1H NMR, FTIR, DSC and GPC techniques. IDV loaded mPEG- PCL nanoparticles prepared by emulsification solvent evaporation method were optimized using D-optimal experimental design and were characterized by various techniques such as DLS, DSC, XRD, AFM and SEM. Using Caco-2 cells as a cellular model, we studied the cellular uptake and transport. Results: In vivo pharmacokinetic studies were performed in rats. The plasma AUC (0-t), t1/2 and Cmax of IDV-mPEG-PCL NPs were increased by 5.30, 5.57 and 1.37 fold compared to the IDV solution, respectively. Conclusion: The results of this study are promising for the use of biodegradable polymeric nanoparticles to improve oral drug delivery.

Keywords: Indinavir; cellular uptake; mPEG-PCL nanoparticle; optimization; oral delivery; transport.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Biological Transport
  • Caco-2 Cells
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Humans
  • Indinavir / administration & dosage*
  • Indinavir / chemistry
  • Indinavir / metabolism
  • Indinavir / pharmacokinetics*
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Tissue Distribution

Substances

  • Drug Carriers
  • Polyesters
  • methoxy poly(ethylene glycol-co-epsilon-caprolactone)
  • Polyethylene Glycols
  • Indinavir