Doxorubicin (DOX) plays an important role in cancer treatment; however, high cardiotoxicity and low penetration in solid tumors are the main limitations of its use. Liposomal formulations have been developed to attenuate the DOX toxicity, but the technological enhancement of the liposomal formulation as well as the addition of another agent with antitumor properties, like alpha-tocopheryl succinate (TS), a semi-synthetic analog of vitamin E, could certainly bring benefits. Thus, in this study, it was proposed the development of liposomes composed of DOX and TS (pHSL-TS-DOX). A new DOX encapsulation method, without using the classic ammonium sulfate gradient with high encapsulation percentage was developed. Analysis of Small Angle X-ray Scattering (SAXS) and release study proved the pH-sensitivity of the developed formulation. It was observed stabilization of tumor growth using pHSL-TS-DOX when compared to free DOX. The toxicity tests showed the safety of this formulation since it allowed body weight initial recovery after the treatment and harmless to heart and liver, main target organs of DOX toxicity. The developed formulation also avoided the occurrence of myelosuppression, a typical adverse effect of DOX. Therefore, pHSL-TS-DOX is a promising alternative for the treatment of breast cancer since it has adequate antitumor activity and a safe toxicity profile.

中文翻译：

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琥珀酸α-生育酚酸酯改善了封装，pH敏感性，抗肿瘤活性并降低了阿霉素脂质体的毒性。

阿霉素（DOX）在癌症治疗中起着重要作用；然而，在实体瘤中高心脏毒性和低渗透是其使用的主要限制。已经开发了脂质体制剂来减轻DOX毒性，但是脂质体制剂的技术增强以及添加另一种具有抗肿瘤特性的药物，例如维生素E的半合成类似物琥珀酸α-生育酚酯（TS），可以当然会带来好处。因此，在本研究中，提出了由DOX和TS（pHSL-TS-DOX）组成的脂质体的开发。开发了一种新的DOX封装方法，该方法不使用具有高封装百分比的经典硫酸铵梯度。对小角X射线散射（SAXS）的分析和释放研究证明了所开发配方的pH敏感性。与游离DOX相比，观察到使用pHSL-TS-DOX使肿瘤生长稳定。毒性测试表明该制剂的安全性，因为它可以使体重在治疗后初步恢复并且对心脏和肝脏（DOX毒性的主要靶器官）无害。开发的制剂还避免了骨髓抑制的发生，骨髓抑制是DOX的典型不良反应。因此，pHSL-TS-DOX具有良好的抗肿瘤活性和安全的毒性，因此是治疗乳腺癌的有前途的替代方法。开发的配方还避免了骨髓抑制的发生，这是DOX的典型不良反应。因此，pHSL-TS-DOX具有良好的抗肿瘤活性和安全的毒性，因此是治疗乳腺癌的有前途的替代方法。开发的配方还避免了骨髓抑制的发生，这是DOX的典型不良反应。因此，pHSL-TS-DOX具有良好的抗肿瘤活性和安全的毒性，因此是治疗乳腺癌的有前途的替代方法。