Chicken embryo model for in vivo acute toxicological and antitumor efficacy evaluation of lipid nanocarrier containing doxorubicin
Aline de Cristo Soares Alves, Danieli Rosane Dallemole, Taiane Medeiro Ciocheta, Augusto Ferreira Weber, Samanta da Silva Gündel, Fernanda Visioli, Fabrício Figueiró, Sı́lvia Stanisçuaski Guterres, Adriana Raffin Pohlmann
Abstract
Nanoencapsulation of chemotherapeutics, including doxorubicin, can endow the formulations with unique properties, such as a decrease in adverse effects and toxicity. The chicken embryo model is an alternative and well-accepted strategy for evaluating the toxicity and efficacy of drugs and nanoformulations. Therefore, this study proposes the development of a new lipid nanocarrier for doxorubicin delivery (NanoLip-Dox) and posterior evaluation of toxicological profile and antitumoral efficacy against a breast tumor in chicken embryos. NanoLip-Dox showed a unimodal particle size (< 150 nm), negative zeta potential (−19.5 mV), absence of drug crystals, drug content of 0.099 mg·mL−1, and high entrapment efficiency (95%). NanoLip-Dox did not cause toxicity in the chicken embryos; in contrast, doxorubicin hydrochloride induced moderate irritation in the chorioallantoic membrane (at 862.1 μmol·L−1), a survival rate of 50% (at 1.7 μmol·L−1), and an increase in aspartate aminotransferase (at 862.1, 344.8, and 172.4 μmol·L−1). In addition, NanoLip-Dox (at 1.7 μmol·L−1) showed potent antitumor efficacy with a high tumor remission percentage (40.9 ± 9.7%) compared to the control group (8.6 ± 14.8%). These findings together with the absence of toxicity concerning morphological characteristics, weights of embryos and organs, hematologic parameters, and enzymatic activity (alanine aminotransferase, aspartate aminotransferase, and creatinine) suggest the safety and efficacy of NanoLip-Dox.