Oral delivery of indinavir using mPEG-PCL nanoparticles: preparation, optimization, cellular uptake, transport and pharmacokinetic evaluation

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 1 H 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), t 1/2 and C max 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.

Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy

“…Several macromolecular structures are being explored as DDS [3,4]. Among them, polymeric nanoparticles (NPs) are considered one of the most promising nanocarriers for use in oncology [5,6,7,8,9,10]. Their building blocks are biodegradable and biocompatible, and their release profiles can be modulated by the polymeric structure itself.…”

The In Vivo Pharmacokinetics of Block Copolymers Containing Polyethylene Glycol Used in Nanocarrier Drug Delivery Systems

“…Therefore, revealing the in vivo fate of PEG-PCL polymers is crucial for its medical application. To date, pharmacokinetic differences in vivo between small molecular drugs and PEG-PCL loaded particles have been extensively studied (Feng et al, 2012;Wang et al, 2014;Manjili et al, 2018;Kurd et al, 2019). However, in vivo fate studies of triblock polymers such as PCL-PEG-PCL or PEG-PCL-PEG have not been reported, only a few studies have This research was supported by the National Natural Science Foundation of China (Grant No.…”

Nanoemulsions: The rising star of antiviral therapeutics and nanodelivery system—current status and prospects

“…The brain uptake clearance of Idv delivered orally via Idv-NEs and lactoferrin-treated Idv-NEs were 393- and 420-times higher compare to the free drug [ 79 ]. Likewise, the oral delivery of Idv loaded methoxypoly (ethyleneglycol)-poly (e-caprolactone) (mPEG-PCL) nanoparticle in the rat showed increased bioavailability of the drug in plasma compared to the Idv solution [ 80 ]. The assembly of multiple retroviral drugs into a single NEs carrier system may empower the effective treatment of HIV infection.…”