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; Fabricio Figueiró; Silvia Stanisçuaski Guterres; Adriana Raffin Pohlmann

doi:10.1016/j.ijpx.2023.100193

Chicken embryo model for in vivo acute toxicological and antitumor efficacy evaluation of lipid nanocarrier containing doxorubicin

Int J Pharm X. 2023 Jun 24:6:100193. doi: 10.1016/j.ijpx.2023.100193. eCollection 2023 Dec 15.

Authors

Aline de Cristo Soares Alves¹, Danieli Rosane Dallemole¹, Taiane Medeiro Ciocheta¹, Augusto Ferreira Weber², Samanta da Silva Gündel¹, Fernanda Visioli^{3

4}, Fabricio Figueiró², Silvia Stanisçuaski Guterres¹, Adriana Raffin Pohlmann¹

Affiliations

¹ Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, 90610-000, RS, Brazil.
² Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS 90035-003, Brazil.
³ Programa de Pós-Graduação em Odontologia, Faculdade de Odontologia, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2492, Porto Alegre, RS 90035-003, Brazil.
⁴ Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil.

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.

Keywords: Alternative animal model; CAM assay; MCF-7 cell line; Nanotechnology; Toxicity; Tumor.