HEBA S. RAMADAN*#, TAHA I. HEWALA**
*Medical Biophysics Department, Medical Research Institute, Alexandria University, 21561, Egypt
**Radiation Sciences Department, Medical Research Institute, Alexandria University, 21561, Egypt
Objective: To evaluate the therapeutic efficacy and cardiotoxicity of galactosylated chitosan nanoparticles containing doxorubicin (DOX-loaded GC-NPs) under the effect of ultrasound irradiation. Materials and Mhodets: DOX-loaded GC-NPs were prepared and characterized before being injected intraperitoneal (i.p.) into mice bearing chemically induced hepatocellular carcinoma (HCC) in the presence and absence of ultrasound irradiation. The other HCC bearing mice were injected i.p. with free DOX in the presence and absence of ultrasound irradiation. For all mice, serum alpha-fetoprotein (AFP) and transforming growth factor-β1 (TGFβ1), hepatic alanine transaminase (ALT) and cardiac aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Results: DOX-loaded GC NPs were having the following criteria: average particle size of 100.4 nm, completely spherical, in the nanoscale with no agglomeration, mean drug loading efficiency (DLE) of 23.26% and mean encapsulation efficiency (EE) of 66.6%. The HCC-bearing mice treated with DOX-loaded GC NPs showed significant decreases in hepatic ALT activity, serum AFP and TGFβ1 levels compared with HCC-bearing mice treated with free DOX which were ameliorated by ultrasound irradiation. Moreover, the HCC-bearing mice treated with DOX-loaded GC-NPs either in the presence or absence of ultrasound irradiation revealed significant declines in the activities of cardiac AST, LDH and CK compared with HCC-bearing mice treated with free DOX and the levels of these cardiotoxicity markers reached their normal values as in the normal control group. Conclusion: It could be concluded that treatment of HCC-bearing mice with DOX-loaded GC-NPs combined with ultrasound irradiation was a better therapeutic modality than free DOX with no cardiotoxicity.
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