engleski

In vivo investigation of inflammatory response of different doxorubicin formulations

Doxorubicin (DOX) is one of the most effective cytotoxic drugs against solid tumors and hematologic malignant diseases. However, the clinical application of DOX is limited due to dose-related toxicity and inflammatory response. In order to reduce toxic side-effects of antitumor agents, nanoformulation were developed as novel drug delivery systems as they may favor accumulation of the drug at tumor sites and consequently reduce its toxicity. The aim of this study was to determine inflammatory effects of DOX administered in three different forms – DOX as free compound solution, a novel delivery system of nanoformulated poly(lactic-co-glycolic acid) (PLGA-DOX), and commercially available DOX encapsulated in liposomal nanoparticles (nanoDOX). These formulations were administrated to male and female Wistar rats four times, once per week, by intraperitoneal application. Expression of inflammation-related genes (IL-6, IL-8, TNFα and IL-1β) in heart, liver and kidney tissue of treated and control rats was evaluated using Real-Time PCR. Free DOX compound significantly increased expression of IL-6 and IL-8 in heart and liver tissue, which supports previously obtained results on DOX cardiotoxicity and liver toxicity. PLGA-DOX increased production of only IL-8 in liver tissue, but did not significantly elevate expression of other inflammation-related genes in heart or kidney tissue, which was similar to results obtained for nanoDOX. Additionally, significant reduction of IL-1 expression in kidney tissue as potential attenuation of inflammatory response was noticed after administration of PLGA-DOX. Therefore, novel PLGA-DOX formulation demonstrated lower inflammatory potential compared to clinically approved nanoDOX and DOX.

doxorubicin, nano formulation, in vivo, inflammatory response

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