• Home
  • Search Results
  • Novel protease inhibitor-loaded Nanoparticle-in-Microparticle Delivery System leads to a dramatic improvement of the oral pharmacokinetics in dogs.

Novel protease inhibitor-loaded Nanoparticle-in-Microparticle Delivery System leads to a dramatic improvement of the oral pharmacokinetics in dogs.

Biomaterials (2014-12-03)
Julieta C Imperiale, Pablo Nejamkin, Maria J Del Sole, Carlos E Lanusse, Alejandro Sosnik
ABSTRACT

With the advent of the Highly Active Antiretroviral Therapy, the morbidity and the mortality associated to HIV have been considerably reduced. However, 35-40 million people bear the infection worldwide. One of the main causes of therapeutic failure is the frequent administration of several antiretrovirals that results in low patient compliance and treatment cessation. In this work, we have developed an innovative Nanoparticle-in-Microparticle Delivery System (NiMDS) comprised of pure drug nanocrystals of the potent protease inhibitor indinavir free base (used as poorly water-soluble model protease inhibitor) produced by nanoprecipitation that were encapsulated within mucoadhesive polymeric microparticles. Pure drug nanoparticles and microparticles were thoroughly characterized by diverse complementary techniques. NiMDSs displayed an encapsulation efficiency of approximately 100% and a drug loading capacity of up to 43% w/w. In addition, mucoadhesiveness assays ex vivo conducted with bovine gut showed that film-coated microparticles were retained for more than 6 h. Finally, pharmacokinetics studies in mongrel dogs showed a dramatic 47- and 95-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the free unprocessed drug. These results support the outstanding performance of this platform to reduce the dose and the frequency of administration of protease inhibitors, a crucial step to overcome the current patient-incompliant therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetone, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Acetone, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%
Sigma-Aldrich
Acetone, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Calcium chloride dihydrate, ACS reagent, ≥99%
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Calcium chloride dihydrate, for molecular biology, ≥99.0%
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
Sigma-Aldrich
Calcium chloride dihydrate, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
Sigma-Aldrich
Calcium chloride dihydrate, ReagentPlus®, ≥99.0%
Sigma-Aldrich
Acetone, Laboratory Reagent, ≥99.5%
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.8%
Supelco
Acetone, analytical standard
Sigma-Aldrich
N,N′-Disuccinimidyl carbonate, ≥95%
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) formic acid, suitable for HPLC
Sigma-Aldrich
Calcium chloride dihydrate, BioXtra, ≥99.0%
Supelco
Acetone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Acetonitrile, suitable for HPLC-GC, ≥99.8% (GC)
Sigma-Aldrich
Acetone, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99% (GC)
Sigma-Aldrich
Calcium chloride dihydrate, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99%
Sigma-Aldrich
Acetone, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetone, histological grade, ≥99.5%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Calcium chloride dihydrate, BioUltra, for molecular biology, ≥99.5% (KT)
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material