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Sequential Drug Release Achieved with Dual-Compartment Microcontainers: Toward Combination Therapy
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-08-12 , DOI: 10.1002/adtp.202200106 Juliane Fjelrad Christfort 1 , Carmen Milián‐Guimerá 1 , Khorshid Kamguyan 1 , Morten Borre Hansen 2, 3 , Line Hagner Nielsen 1 , Lasse Højlund Eklund Thamdrup 1 , Kinga Zór 1 , Anja Boisen 1
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-08-12 , DOI: 10.1002/adtp.202200106 Juliane Fjelrad Christfort 1 , Carmen Milián‐Guimerá 1 , Khorshid Kamguyan 1 , Morten Borre Hansen 2, 3 , Line Hagner Nielsen 1 , Lasse Højlund Eklund Thamdrup 1 , Kinga Zór 1 , Anja Boisen 1
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Combination drug therapy is commonly used to treat cancer, diabetes, cardiovascular conditions, and infections. However, these therapies face challenges associated with patient compliance and toxicology. Over the past decades, microdevices have emerged as a promising candidate for oral delivery allowing for targeted drug delivery with a tunable drug release. In the present work, engineered and monodisperse dual-compartment microdevices are developed to achieve a physical separation of two drugs followed by a sequential release in the gastrointestinal tract. As proof-of-concept, the compartments are sealed with two pH-sensitive polymers of different thicknesses to control the sequential release of propranolol and furosemide. In vitro release studies and in vivo absorption studies in rats confirm a sequential drug release from the two compartments. Unlike other proposed approaches, it is highly advantageous that the drugs can be loaded directly as powders, and that their release can be tuned via optimized coatings to achieve the desired release and absorption profiles. Conclusively, this study lays a strong foundation for the future use of microdevices to enable co-delivery of drugs followed by a sequential release in close proximity in the gastrointestinal tract.
中文翻译：
双隔室微容器实现序贯药物释放：走向联合治疗
联合药物疗法通常用于治疗癌症、糖尿病、心血管疾病和感染。然而，这些疗法面临着与患者依从性和毒理学相关的挑战。在过去的几十年中，微型装置已成为口服给药的有前途的候选者，可以通过可调的药物释放进行靶向给药。在目前的工作中，开发了工程化和单分散双隔室微型装置，以实现两种药物的物理分离，然后在胃肠道中顺序释放。作为概念验证，隔室用两种不同厚度的 pH 敏感聚合物密封，以控制普萘洛尔和呋塞米的顺序释放。在大鼠中进行的体外释放研究和体内吸收研究证实药物从两个隔室连续释放。与其他提议的方法不同，药物可以直接作为粉末加载，并且可以通过优化的涂层调整它们的释放以实现所需的释放和吸收曲线，这是非常有利的。总而言之，这项研究为未来使用微型设备实现药物联合输送以及随后在胃肠道中紧邻顺序释放奠定了坚实的基础。
更新日期：2022-08-12
中文翻译：
双隔室微容器实现序贯药物释放：走向联合治疗
联合药物疗法通常用于治疗癌症、糖尿病、心血管疾病和感染。然而，这些疗法面临着与患者依从性和毒理学相关的挑战。在过去的几十年中，微型装置已成为口服给药的有前途的候选者，可以通过可调的药物释放进行靶向给药。在目前的工作中，开发了工程化和单分散双隔室微型装置，以实现两种药物的物理分离，然后在胃肠道中顺序释放。作为概念验证，隔室用两种不同厚度的 pH 敏感聚合物密封，以控制普萘洛尔和呋塞米的顺序释放。在大鼠中进行的体外释放研究和体内吸收研究证实药物从两个隔室连续释放。与其他提议的方法不同，药物可以直接作为粉末加载，并且可以通过优化的涂层调整它们的释放以实现所需的释放和吸收曲线，这是非常有利的。总而言之，这项研究为未来使用微型设备实现药物联合输送以及随后在胃肠道中紧邻顺序释放奠定了坚实的基础。
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