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用于靶向肺部给药的果胶基水凝胶微球的设计

Design of Pectin-Based Hydrogel Microspheres for Targeted Pulmonary Delivery.

作者信息

Chai Andy, Schmidt Keagan, Brewster Gregory, Xiong Lu Shi Peng, Church Benjamin, Wahl Timothy, Sadabadi Hamed, Kumpaty Subha, Zhang Wujie

机构信息

Department of Chemistry, Rhodes College, Memphis, TN 38112, USA.

Chemical and Biomolecular Engineering Program, Department of Physics and Chemistry, Milwaukee School of Engineering, Milwaukee, WI 53202, USA.

出版信息

Gels. 2023 Sep 1;9(9):707. doi: 10.3390/gels9090707.

Abstract

Pulmonary drug delivery via microspheres has gained growing interest as a noninvasive method for therapy. However, drug delivery through the lungs via inhalation faces great challenges due to the natural defense mechanisms of the respiratory tract, such as the removal or deactivation of drugs. This study aims to develop a natural polymer-based microsphere system with a diameter of around 3 μm for encapsulating pulmonary drugs and facilitating their delivery to the deep lungs. Pectin was chosen as the foundational material due to its biocompatibility and degradability in physiological environments. Electrospray was used to produce the pectin-based hydrogel microspheres, and Design-Expert software was used to optimize the production process for microsphere size and uniformity. The optimized conditions were determined to be as follows: pectin/PEO ratio of 3:1, voltage of 14.4 kV, distance of 18.2 cm, and flow rate of 0.95 mL/h. The stability and responsiveness of the pectin-based hydrogel microspheres can be altered through coatings such as gelatin. Furthermore, the potential of the microspheres for pulmonary drug delivery (i.e., their responsiveness to the deep lung environment) was investigated. Successfully coated microspheres with 0.75% gelatin in 0.3 M mannitol exhibited improved stability while retaining high responsiveness in the simulated lung fluid (Gamble's solution). A gelatin-coated pectin-based microsphere system was developed, which could potentially be used for targeted drug delivery to reach the deep lungs and rapid release of the drug.

摘要

通过微球进行肺部药物递送作为一种非侵入性治疗方法,已引起越来越多的关注。然而,由于呼吸道的天然防御机制,如药物的清除或失活,通过吸入经肺给药面临巨大挑战。本研究旨在开发一种基于天然聚合物的微球系统,其直径约为3μm,用于包裹肺部药物并促进其递送至深部肺组织。由于果胶在生理环境中的生物相容性和可降解性,选择其作为基础材料。采用电喷雾法制备果胶基水凝胶微球,并使用Design-Expert软件优化微球尺寸和均匀性的生产工艺。确定的优化条件如下:果胶/聚氧化乙烯比例为3:1、电压为14.4 kV、距离为18.2 cm、流速为0.95 mL/h。果胶基水凝胶微球的稳定性和响应性可通过明胶等涂层来改变。此外,还研究了微球用于肺部药物递送的潜力(即它们对深部肺环境的响应性)。在0.3 M甘露醇中成功包被0.75%明胶的微球在模拟肺液(甘布尔溶液)中表现出提高的稳定性,同时保持高响应性。开发了一种明胶包被的果胶基微球系统,其有可能用于靶向药物递送以到达深部肺组织并实现药物的快速释放。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de22/10529711/fc637637a9cf/gels-09-00707-sch001.jpg

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