[Biodistribution of Rifabutin Polymeric Transport Form].
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, 7h, 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 polymerform (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).


CONCLUSIONS
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.
I G
IG
Kuznetsova
E G
EG
Dubovik
N S
NS
Dubovik
T N
TN
Komarov
Y V
YV
Medvedev
L A
LA
Menshikova
S E
SE
Severin
I E
IE
Shohin
T A
TA
Yarushok
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D058726:Nanoconjugates; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D017828:Rifabutin / Q000008:administration & dosage / Q000493:pharmacokinetics; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D058726:Nanoconjugates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017828:Rifabutin; D011100:Polyglycolic Acid; D019344:Lactic Acid