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OJVRTM
Online Journal of Veterinary Research ©
Volume 24(12): 699-715,
2020.
Pharmacokinetics
and hepatotoxicity of flutamide liposomes after IV
administration in Wistar rats
Umrethia ML, Ghosh PK, Majithiya
RJ, Murthy RSR.
Drug
Delivery Research Laboratory, Pharmacy Department, The
M.S. University of Baroda,
Vadodara, India
ABSTRACT
Umrethia ML, Ghosh PK, Majithiya RJ, Murthy RSR.,
Pharmacokinetics and hepatotoxicity of flutamide
liposomes after IV administration in male Wistar
rats, Onl J Vet Res., 24(12): 699-715, 2020. Flutamide (FLT) is a non-steroidal anti-androgenic used
for treatment of prostate cancer. However, high doses can be hepatotoxic. We encapsulated FLT with stealth liposomes
(CL) with normal liposomes (SL) to evaluate pharmacokinetics, reduce uptake and
hepatotoxicity. FLT was encapsulated CL with stealth liposome egg phosphotidylcholine (ePC) and
cholesterol by thin film hydration followed by high-pressure homogenization.
For liposomes, methoxy polyethylene glycol
2000-phosphotidyl ethanolamine (mPEG2000-PE) was added to enhance
hydrophilicity. We found that smaller particles (136 nm) with EE of 99.28% were
less stable than larger ones (158 nm) with EE of 98.54% in human plasma at
37șC. Encapsulated flutamide was retained 36h whereas
free drug or normal liposomes only 2-6h. Plasma half life,
Vss, MRT and AUC for FLT was ~2-10 fold
higher for stealth liposomes compared with normal liposomes and free drug. Flutamide in all organs was ~75-82% less (P < 0.01)
using stealth liposomes compared with free drug or normal liposomes.
Histopathological studies and Alanine transaminase (ALT) analysis confirmed
that stealth liposomes reduced tioxicity of flutamide in Wistar rats.
Keywords: Flutamide, liposomes, pharmacokinetics, biodistribution,
histopathology.
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