化疗药物的纳米封装,包括阿霉素,可以赋予配方独特的性能,例如减少副作用和毒性。鸡胚模型是用于评估药物和纳米制剂的毒性和功效的替代且广为接受的策略。因此,这项研究提出了一种用于多柔比星递送的新型脂质纳米载体(NanoLip-Dox)的开发以及对鸡胚胎中乳腺肿瘤的毒理学特征和抗肿瘤功效的后验评估。NanoLip-Dox显示单峰粒径(<150nm),负ζ电位(-19.5mV),没有药物晶体,药物含量为0.099mg·mL-1,包封率高(95%)。NanoLip-Dox对鸡胚没有毒性;相反,盐酸多柔比星对绒毛尿囊膜(862.1μmol·L-1)产生中度刺激,存活率为50%(在1.7μmol·L-1时),天冬氨酸转氨酶增加(862.1、344.8和172.4μmol·L-1)。此外,NanoLip-Dox(1.7μmol·L-1)显示出有效的抗肿瘤功效,与对照组(8.6±14.8%)相比,肿瘤缓解率高(40.9±9.7%)。这些发现加上没有关于形态特征的毒性,胚胎和器官的重量,血液学参数,和酶活性(丙氨酸转氨酶,天冬氨酸转氨酶,和肌酐)提示NanoLip-Dox的安全性和有效性。
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.