Pharmaceutics
(Dec 2018)
Enhanced Delivery of 4-Thioureidoiminomethylpyridinium Perchlorate in Tuberculosis Models with IgG Functionalized 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
Affiliations
- Leonid Churilov
- Faculty of Medicine, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Viktor Korzhikov-Vlakh
- Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Ekaterina Sinitsyna
- Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Dmitry Polyakov
- Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Oleg Darashkevich
- Republican Center for Innovative and Technical Creativity, Slavinskogo str. 12, 220086 Minsk, Belarus
- Mikhail Poida
- Faculty of Medicine, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Galina Platonova
- Institute of Macromolecular Compounds, Russian Academy of Sciences, Bolshoi pr. V.O. 31, 199004 St. Petersburg, Russia
- Tatiana Vinogradova
- St. Petersburg Research Institute of Phthisiopulmonology, Polytechnical str. 32, 194064, St. Petersburg, Russia
- Vladimir Utekhin
- Faculty of Medicine, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Natalia Zabolotnykh
- St. Petersburg Research Institute of Phthisiopulmonology, Polytechnical str. 32, 194064, St. Petersburg, Russia
- Vsevolod Zinserling
- Faculty of Medicine, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Peter Yablonsky
- Faculty of Medicine, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Arto Urtti
- Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- Tatiana Tennikova
- Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, Russia
- DOI
-
https://doi.org/10.3390/pharmaceutics11010002
- Journal volume & issue
-
Vol. 11,
no. 1
p.
2
Abstract
Read online
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.
Keywords
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