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

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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
Publication statusPublished - 1 Jan 2019

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Tuberculosis
Immunoglobulin G
Nanoparticles
Camelus
Pharmaceutical Preparations
Drug Compounding
Multiple Drug Resistance
Drug Delivery Systems
Drug-Related Side Effects and Adverse Reactions
Sodium Chloride
Liquid Chromatography
Fluorescent Antibody Technique
Mass Spectrometry
Suspensions
Macrophages
Lung
poly(lactic acid)
perchlorate
Therapeutics

Scopus subject areas

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

Cite this

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title = "Enhanced delivery of 4-2 thioureidoiminomethylpyridinium perchlorate in 3 tuberculosis models with IgG functionalized 4 poly(lactic acid) based particles",
abstract = "The compound 4-thioureidoiminomethylpyridinium perchlorate (perchlozone{\circledC}) 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.",
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author = "Leonid Churilov and Viktor Korzhikov-Vlakh and Ekaterina Sinitsyna and Dmitry Polyakov and Oleg Darashkevich and Mikhail Poida and Galina Platonova and Tatiana Vinogradova and Vladimir Utekhin and Natalia Zabolotnykh and Vsevolod Zinserling and Peter Yablonsky and Arto Urtti and Tatiana Tennikova",
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doi = "10.3390/pharmaceutics11010002",
language = "English",
volume = "11",
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publisher = "MDPI AG",
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Enhanced delivery of 4-2 thioureidoiminomethylpyridinium perchlorate in 3 tuberculosis models with IgG functionalized 4 poly(lactic acid) based particles. / Churilov, Leonid ; Korzhikov-Vlakh, Viktor ; Sinitsyna, Ekaterina; Polyakov, Dmitry ; Darashkevich, Oleg ; Poida, Mikhail ; Platonova, Galina ; Vinogradova, Tatiana ; Utekhin, Vladimir ; Zabolotnykh, Natalia ; Zinserling, Vsevolod ; Yablonsky, Peter ; Urtti , Arto ; Tennikova, Tatiana .

In: Pharmaceutics, Vol. 11, No. 1, 2, 01.01.2019, p. 1-20.

Research output

TY - JOUR

T1 - Enhanced delivery of 4-2 thioureidoiminomethylpyridinium perchlorate in 3 tuberculosis models with IgG functionalized 4 poly(lactic acid) based particles

AU - Churilov, Leonid

AU - Korzhikov-Vlakh, Viktor

AU - Sinitsyna, Ekaterina

AU - Polyakov, Dmitry

AU - Darashkevich, Oleg

AU - Poida, Mikhail

AU - Platonova, Galina

AU - Vinogradova, Tatiana

AU - Utekhin, Vladimir

AU - Zabolotnykh, Natalia

AU - Zinserling, Vsevolod

AU - Yablonsky, Peter

AU - Urtti , Arto

AU - Tennikova, Tatiana

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - 4-thioureidoiminomethylpyridinium perchlorate (perchlozone)

KW - Camel mini-antibodies

KW - Drug delivery

KW - Macrophage

KW - Opsonization

KW - Poly(lactide)

KW - Polymeric nanoparticles

KW - Tuberculosis

KW - 4

KW - antibodies

KW - camel mini

KW - drug delivery

KW - macrophage

KW - opsonization

KW - poly(lactide)

KW - polymeric nanoparticles

KW - thioureidoiminomethylpyridinium perchlorate (perchlozone)

KW - tuberculosis

KW - PHAGOCYTOSIS

KW - MICROSPHERES

KW - DRUG-DELIVERY

KW - RIFAMPICIN

KW - FORMULATION

KW - MICROPARTICLES

KW - 4-thioureidoiminomethylpyridinium perchlorate (perchlozone)

KW - IN-VITRO

KW - SURFACE

KW - ALVEOLAR MACROPHAGES

KW - INFECTION

KW - camel mini-antibodies

UR - http://www.scopus.com/inward/record.url?scp=85059319241&partnerID=8YFLogxK

UR - http://www.mdpi.com/1999-4923/11/1/2

UR - http://www.mendeley.com/research/enhanced-delivery-4thioureidoiminomethylpyridinium-perchlorate-tuberculosis-models-igg-functionalize

U2 - 10.3390/pharmaceutics11010002

DO - 10.3390/pharmaceutics11010002

M3 - Article

AN - SCOPUS:85059319241

VL - 11

SP - 1

EP - 20

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

M1 - 2

ER -