BIODISTRIBUTION OF RIFABUTIN POLYMERIC TRANSPORT FORM

Cover Page

Abstract

Background: One way to increase drug efficacy is to provide a drug delivery transport system to the target organ. A widely used method is to incorporate the drug in a biodegradable polymer composition with forming nanosized drug’s transport forms. Objective: Our aim was to investigate the tissue biodistribution of antibiotic rifabutin transport system based on lactic and glycolic acids copolymer, and to compare it with the pure substance of rifabutin. Methods: These substances were administered to two groups of rats intragastrically in the doses of 10 mg/kg. After a certain period of time, the animals were sacrificed by cervical dislocation. Samples preparation for analysis was carried out of the liquid-liquid extraction. Active substance’s concentrations were measured by high performance liquid chromatography method. Results: The study included 8-week-aged Wistar rats of both sexes weighing 0.22±0.02 kg. Animals were divided into 2 groups. The study group received polymer form of antibiotic, and the comparison group received substance of rifabutin. In intervals of 10 min, 30 min, 1 h, 2 h, 4 h, 7 h, 15 h, 24 h after drug administration liver, lung, spleen, kidney, intestines, stomach, heart and brain were resected respectively. Organs were measured by their weight. The drug was not detected in the brain. Rifabutin was determined in other examined tissues within 10 minutes and the maximum drug concentration in organs was fixed in 1.5–3.5 hours after administration. The rifabutin concentrations defined in the lungs were significantly higher in polymer form (p <0.05). The polymer form’s distribution coefficient was higher in the liver and lungs (15.83 and 10.14 μg/g respectively) in comparison with the substance one. The minimum amount of the active ingredient was observed in the heart (0.02 μg/g). Conclusion: It is shown that the inclusion of the drug in a polymeric form substantially alters its localization in organs and tissues. Extensive biodistribution nanorifabutin in lung tissue, liver and spleen is established.

 

 

About the authors

I. G. Kuznetsova

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Author for correspondence.
Email: irina1105@rambler.ru

старший преподаватель кафедры биологической химии лечебного факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 609-14-00, доб. 3145

Russian Federation

E. G. Dubovik

Lomonosov Moscow State University, Moscow, Russian Federation

Email: dubovik@mail.ru

аспирант кафедры биоинженерии биологического факультета МГУ им. М.В. Ломоносова
Адрес: 119234, Москва, Ленинские горы, д. 1, тел.: +7 (495) 939-10-00, доб. 2401

Russian Federation

N. S. Dubovik

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: berezanatawa@yandex.ru

кандидат фармацевтических наук, ассистент кафедры фармацевтической химии фармацевтического факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 609-14-00, доб. 1636

Russian Federation

T. N. Komarov

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: t.n.komarov@yandex.ru

кандидат фармацевтических наук, ассистент кафедры фармацевтической химии
фармацевтического факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 128-57-00

Russian Federation

Yu. V. Medvedev

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: y125195@yandex.ru

кандидат фармацевтических наук, старший преподаватель кафедры
фармацевтической химии фармацевтического факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 128-57-00

Russian Federation

L. A. Men'shchikova

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: lily-chka@mail.ru

аспирант кафедры фармацевтической химии фармацевтического факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 128-57-00

Russian Federation

S. E. Severin

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: sergsev@inbox.ru

член-корреспондент РАН, профессор, заведующий кафедрой биологической химии
лечебного факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (499) 613-23-20

Russian Federation

I. E. Shokhin

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: sovdep2007@yandex.ru

кандидат фармацевтических наук, старший преподаватель кафедры фармацевтической химии фармацевтического факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 128-57-00

Russian Federation

T. A. Yarushok

Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: doctormarmalade@mail.ru

кандидат фармацевтических наук, ассистент кафедры фармацевтической химии
фармацевтического факультета Первого МГМУ им. И.М. Сеченова
Адрес: 119048, Москва, ул. Трубецкая, д. 8, стр. 2, тел.: +7 (495) 128-57-00

Russian Federation

References

  1. Kunin C.M. Antimicrobial activity of rifabutin. Clin. Infect. Dis. 1996; 22 (Suppl. 1): 3–14.
  2. Chaisson R.E. Potential role of rifabutin in prophylaxis for tuberculosis and infections due to multiple opportunistic pathogens. Clin. Infect.Diseases. 1996; 22: 61–69.
  3. Griffith D.E. Risk-Benefit Assessment of Therapies for Myco-bacterium avium Complex Infections. Drug Safety. 1999; 21 (2): 137–152.
  4. Kulkarni P.R., Yadav J.D., Vaidya K.A. Liposomes: a novel drug delivery system. Int. J. Curr. Pharmaceutic. Res. 2011; 3 (2): 10–18.
  5. Prikaz MZ RF № 708n ot 23.08.2010 g. «Pravila laboratornoi praktiki» (Order of the Ministry of Health of the Russian Federation № 708n "Regulations of Laboratory Practice" dated 23.08.2010). Available at: http://www.rg.ru/2010/10/22/laboratornaya-praktika-dok.html (accessed: 05.03.2015).
  6. Kuznetsova I.G., Severin S.E. Using lactic and glycolic acids to produce nanoscale formulations. Razrabotka i registratsiya lekarstvennykh sredstv = Development and registration of drugs. 2013;4:30–37.
  7. Kaur J., Muttil P., Verma R.K., Kumar K., Yadav A.B., Sharma R., Misra A. A hand-held apparatus for «nose-only» exposure of mice to inhalable microparticles as a dry powder inhalation targeting lung and airway macrophages. Eur. J. Pharm. Sci. 2008; 7 (4–5): 351.
  8. Verma R.K., Kaur J., Kumar K., Yadav A.B., Misra A. Intracellular time course, pharmacokinetics, and biodistribution of isoniazid and rifabutin following pulmonary delivery of inhalable microparticles to mice. Antimicrob. Agents Chemother. 2008; 52 (9): 3195–3201.
  9. Kumar V.R., Mukker J.K., Singh R.S., Kumar K., Verma P.R., Misra A. Partial biodistribution and pharmacokinetics of isoniazid and rifabutin following pulmonary delivery of inhalable microparticles to rhesus macaques. Mol. Pharm. 2012; 2; 9 (4): 1011–1016.
  10. Koudriakova T., Iatsimirskaia E., Tulebaev S., Spetie D., Utkin I., Mullet D., Thompson T., Vouros P., Gerber N. In vivo disposition and metabolism by liver and enterocyte microsomes of the antitubercular drug rifabutin in rats. J. Pharm. Exp. Ther. 1996; 279 (3): 1300–1309.
  11. Card J.W., Zeldin D.C., Bonner J.C., Nestmann E.R. Pulmonary applications and toxicity of engineered nanoparticles. Am. J. Physiol. Lung Cell Mol. Physiol. 2008; 295: 400–411.
  12. Benedetti M.S. Inducing properties of rifabutin and effects on the pharmacokinetics and metabolism of concomitant drugs. Pharm. Res. 1995; 32 (4): 177–187.

Statistics

Views

Abstract: 1020

PDF (Russian): 379

Article Metrics

Metrics Loading ...

Dimensions

PlumX


Copyright (c) 2015 Russian academy of sciences



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies