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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations
4 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number2
Pages (from-to)1-20
Number of pages21
JournalPharmaceutics
Volume11
Issue number1
Early online date24 Dec 2018
DOIs
StatePublished - 1 Jan 2019

Scopus subject areas

  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Keywords

  • 4
  • antibodies
  • camel mini
  • drug delivery
  • macrophage
  • opsonization
  • poly(lactide)
  • polymeric nanoparticles
  • thioureidoiminomethylpyridinium perchlorate (perchlozone)
  • tuberculosis
  • PHAGOCYTOSIS
  • MICROSPHERES
  • DRUG-DELIVERY
  • RIFAMPICIN
  • FORMULATION
  • MICROPARTICLES
  • 4-thioureidoiminomethylpyridinium perchlorate (perchlozone)
  • IN-VITRO
  • SURFACE
  • ALVEOLAR MACROPHAGES
  • INFECTION
  • camel mini-antibodies

Fingerprint Dive into the research topics of 'Enhanced delivery of 4-2 thioureidoiminomethylpyridinium perchlorate in 3 tuberculosis models with IgG functionalized 4 poly(lactic acid) based particles'. Together they form a unique fingerprint.

Cite this