Research output: Contribution to journal › Article › peer-review
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: Contribution to journal › Article › peer-review
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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 -
ID: 36328176