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Ultrasonic waves improves the tumoricidal effect of 5-flurouracil loaded on polymeric nanoparticles in chemically induced hepatocellular carcinoma in mice

Heba S.Ramadan, Safia M.Hassan, Amany I.Youssef, Moustafa M.Mohamed, Nelly M.Dabbour

A relatively novel strategy for drug delivery enhancement is application of polymeric nanoparticles in combination with relatively low-intensity ultrasound (US). Bovine serum albumin nanoparticles (BSA NPs) were prepared using intermittent desolvation method and investigated in combinationwith ultrasound irradiation as drug delivery systemto improve the therapeutic efficacy of 5-flurouracil (5-FU) against experimentally induced hepatocellular carcinoma inmice by 4-dimethylaminoazobenzene (DAB) and phenobarbital (PB). The prepared BSANPs encapsulating 5-FU were prepared withmean particle size of 70 nmand spherical in shape. The in vitro drug release studies revealed an enhanced and controlled release of 5-FU from BSA NPs under the effect of ultrasound. Respecting results, mice bearing hepatocellular carcinoma (HCC) and injected with BSA NPs encapsulating 5-FUand irradiated with ultrasonicwaves showed significant decreased levels of hepatic malondialdehyde (MDA) and hepatic alanine transaminase (H.ALT), serum aspartate transaminase (AST) and serum alanine transaminase (ALT).Histopathological examination showed increase in apoptosis, appearance ofmore or less normal cells andwell defined liver cords. Regarding immunohistochemical results, alpha-fetoprotein (AFP) showedmoderate positivity in hepatocytoplasm. Our results nominate BSA NPs in combined with a local ultrasonic irradiation of the tumor to be a powerful new and non-invasive tool of drug targeting and treatment of cancerous tumors.