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  • 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
要旨

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.

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アセトニトリル, suitable for HPLC, gradient grade, ≥99.9%
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アセトン, ACS reagent, ≥99.5%
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アセトン, suitable for HPLC, ≥99.9%
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アセトン, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%
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塩化カルシウム 二水和物, ACS reagent, ≥99%
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アセトン, Laboratory Reagent, ≥99.5%
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アセトニトリル, ACS reagent, ≥99.5%
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アセトニトリル, for HPLC, for UV, ≥99.9% (GC)
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アセトニトリル, suitable for HPLC, gradient grade, ≥99.9%
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塩化カルシウム 二水和物, ReagentPlus®, ≥99.0%
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アセトン, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)
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塩化カルシウム 二水和物, for molecular biology, ≥99.0%
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塩化カルシウム 二水和物, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
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アセトン, suitable for HPLC, ≥99.8%
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アセトニトリル, suitable for HPLC-GC, ≥99.8% (GC)
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アセトン, ACS reagent, ≥99.5%
USP
アセトン, United States Pharmacopeia (USP) Reference Standard
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N,N′-ジスクシンイミジルカルボナート, ≥95%
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アセトン, JIS special grade, ≥99.5%
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塩化カルシウム 二水和物, BioUltra, for molecular biology, ≥99.5% (KT)
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アセトニトリル, anhydrous, 99.8%
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塩化カルシウム 二水和物, puriss., meets analytical specification of Ph. Eur., USP, FCC, E509, 99-103%, ≤0.0001% Al
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アセトン, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99% (GC)
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アセトン, ≥99%, meets FCC analytical specifications
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