In vitro assessment of nanomedicines' propensity to cause palmar-plantar erythrodysesthesia: A Doxil vs. doxorubicin case study

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-08-22 DOI:10.1016/j.nano.2024.102780
Edward Cedrone B.S. , Abbas Ishaq Ph.D. , Emma Grabarnik Ph.D. , Elijah Edmondson DVM., Ph.D. , Sarah Skoczen M.S. , Barry W. Neun B.S. , Matthew Freer Ph.D. , Siannah Shuttleworth M.Res. , Lisbet Sviland M.D., Ph.D. , Anne Dickinson Ph.D. , Marina A. Dobrovolskaia Ph.D.
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Abstract

Palmar-plantar erythrodysesthesia (PPE), also known as hand and foot syndrome, is a condition characterized by inflammation-mediated damage to the skin on the palms and soles of the hands and feet. PPE limits the successful therapeutic applications of anticancer drugs. However, identifying this toxicity during preclinical studies is challenging due to the lack of accurate in vitro and in vivo animal-based models. Therefore, there is a need for reliable models that would allow the detection of this toxicity early during the drug development process. Herein, we describe the use of an in vitro skin explant assay to assess traditional DXR, Doxil reference listed drug (RLD) and two generic PEGylated liposomal DXR formulations for their abilities to cause inflammation and skin damage. We demonstrate that the results obtained with the in vitro skin explant assay model for traditional DXR and Doxil correlate with the clinical data.

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体外评估纳米药物导致掌跖红斑痛的倾向:Doxil与多柔比星对比案例研究。
掌跖红肿症(PPE)又称手足综合征,是一种以炎症介导的手掌和足底皮肤损伤为特征的疾病。PPE 限制了抗癌药物的成功治疗应用。然而,由于缺乏准确的体外和体内动物模型,在临床前研究中识别这种毒性具有挑战性。因此,有必要建立可靠的模型,以便在药物开发过程中及早发现这种毒性。在此,我们介绍了使用体外皮肤外植体检测法来评估传统的 DXR、多西尔参比上市药物(RLD)和两种通用的 PEG 化脂质体 DXR 制剂引起炎症和皮肤损伤的能力。我们证明,传统 DXR 和多西尔的体外皮肤外植体检测模型得出的结果与临床数据相关。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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