Enhanced delivery of 4-2 thioureidoiminomethylpyridinium perchlorate in 3 tuberculosis models with IgG functionalized 4 poly(lactic acid) based particles

Leonid Churilov, Viktor Korzhikov-Vlakh, Ekaterina Sinitsyna, Dmitry Polyakov, Oleg Darashkevich, Mikhail Poida, Galina Platonova, Tatiana Vinogradova, Vladimir Utekhin, Natalia Zabolotnykh, Vsevolod Zinserling, Peter Yablonsky, Arto Urtti , Tatiana Tennikova

Результат исследований: Научные публикации в периодических изданияхстатья

2 Цитирования (Scopus)
2 Загрузки (Pure)

Аннотация

The compound 4-thioureidoiminomethylpyridinium perchlorate (perchlozone©) is a novel anti-tuberculosis drug that is active in multiple drug resistance cases, but the compound is hepatotoxic. To decrease the systemic load and to achieve targeting, we encapsulated the drug into poly(lactic acid)-based micro-(1100 nm) and nanoparticles (170 nm) that were modified with single-chain camel immunoglobulin G (IgG) for targeting. Both micro-and nanoparticles formed stable suspensions in saline solution at particle concentrations of 10–50 mg/mL. The formulations were injected intraperitoneally and intravenously into the mice with experimental tuberculosis. The survival of control animals was compared to that of mice which were treated with daily oral drug solution, single intraperitoneal administration of drug-loaded particles, and those treated both intravenously and intraperitoneally by drug-loaded particles modified with polyclonal camel IgGs. The distribution of particles in the organs of mice was analyzed with immunofluorescence and liquid chromatography/mass spectrometry. Morphological changes related to tuberculosis and drug toxicity were registered. Phagocytic macrophages internalized particles and transported them to the foci of tuberculosis in inner organs. Nanoparticle-based drug formulations, especially those with IgG, resulted in better survival and lower degree of lung manifestations than the other modes of treatment.

Язык оригиналаанглийский
Номер статьи2
Страницы (с-по)1-20
Число страниц21
ЖурналPharmaceutics
Том11
Номер выпуска1
Ранняя дата в режиме онлайн24 дек 2018
DOI
СостояниеОпубликовано - 1 янв 2019

Предметные области Scopus

  • Иммунология и микробиология (все)
  • Фармакология, токсикология и фармацевтика (все)

Ключевые слова

  • 4-thioureidoiminomethylpyridinium perchlorate (perchlozone)
  • Camel mini-antibodies
  • Drug delivery
  • Macrophage
  • Opsonization
  • Poly(lactide)
  • Polymeric nanoparticles
  • Tuberculosis

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