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首页> 外文学位 >Polymeric drug delivery systems: Lidocaine microspheres for prolonged and localized in vivo anesthetic effects and light-induced drug release from polymeric device mediated by bacteriorhodopsin.
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Polymeric drug delivery systems: Lidocaine microspheres for prolonged and localized in vivo anesthetic effects and light-induced drug release from polymeric device mediated by bacteriorhodopsin.

机译：聚合物药物递送系统：利多卡因微球可延长和定位体内麻醉作用，并由细菌视紫红质介导的光诱导药物从聚合物装置中释放。

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摘要

Polymers have been studied in controlling drug release for decades. They can be used to encapsulate drugs for the purpose of sustaining drug release or achieving intelligent drug release. In this dissertation, we explored both applications of the polymer system. First, we fabricated poly(lactide-co-glycolide) (PLGA)-based microspheres loaded with lidocaine in an attempt to prolong anesthetic effects locally at the site of surgical operation to relieve pain. Current treatment protocol for postoperative pain is to infuse anesthetic solution around nerves or into the epidural space. This clinical practice is beset by the short duration of the anesthetic effect unless the continuous infusion is adopted. A continuous infusion, however, requires hospitalization of the patients, thereby increasing associated medical costs. In addition, it may also cause systemic accumulation of the drug, leading to toxic effects. In the first part of dissertation, we demonstrated the extended in vivo anesthetic effects using PLGA-based lidocaine microspheres. The in vivo effects were assessed in a rat model using sciatic nerve blockade. The formulated microspheres loaded with lidocaine achieved a five-hour anesthetic effect compared to that of only one hour by lidocaine solution. To further prolong the effects, we formulated microspheres with poloxamer 407, a thermal sensitive material that gelled at physiological temperature but remained as a solution at cold temperatures such as 4°C. With this microsphere-gel system, the in vivo anesthetic effects were further extended to 8 hours using the same lidocaine dose.; The second part of this dissertation is to fabricate an intelligent polymer-based drug delivery system that releases drugs in response to external stimuli such as light. Polymers responsive to pH changes have been extensively investigated but have limited applicability due to the constancy of physiological pH. Herein we presented the use of bacteriorhodopsin (bR), a transmembrane protein from Halobacterium halobium that transports proton across the cell membrane upon light illumination around 569nm, to induce environmental pH changes upon light exposure. Combining this bR system with a pH-sensitive polymer that swells to release drugs upon the environmental pH changes, light-induced drug release from a one-compartment device made of the pH sensitive polymer was demonstrated.
机译：在控制药物释放方面已经研究了聚合物数十年。它们可用于封装药物，以维持药物释放或实现智能药物释放。在本文中，我们探讨了聚合物体系的两种应用。首先，我们制备了载有利多卡因的聚（丙交酯-共-乙交酯）（PLGA）基微球，以试图延长外科手术部位的局部麻醉效果以减轻疼痛。当前用于术后疼痛的治疗方案是将麻醉剂注入神经周围或硬膜外腔。除非采用连续输注，否则这种临床实践会因麻醉效果持续时间短而困扰。然而，连续输注需要患者住院治疗，从而增加相关的医疗费用。另外，它也可能引起药物的全身蓄积，导致毒性作用。在论文的第一部分中，我们证明了使用基于PLGA的利多卡因微球具有扩展的体内麻醉作用。使用坐骨神经阻滞在大鼠模型中评估了体内作用。装有利多卡因的配制微球达到了五小时的麻醉效果，而利多卡因溶液只有一小时的麻醉效果。为了进一步延长效果，我们用泊洛沙姆407配制了微球，泊洛沙姆407是一种热敏材料，在生理温度下会胶凝，但在4°C等低温下仍为溶液。使用这种微球凝胶系统，使用相同的利多卡因剂量，体内麻醉作用进一步延长至8小时。本论文的第二部分是制造一种基于聚合物的智能药物输送系统，该系统可响应外界刺激（例如光）释放药物。响应pH值变化的聚合物已被广泛研究，但由于生理pH值的恒定性，其适用性有限。在这里，我们介绍了细菌视紫红质（bR），一种来自盐杆菌的跨膜蛋白的用途，该蛋白在569nm左右的光照下通过细胞膜转运质子，从而在曝光后引起环境pH的变化。将此bR系统与在环境pH值变化时会膨胀以释放药物的pH敏感聚合物结合使用，证明了光诱导的药物从pH敏感聚合物制成的单室设备中释放。

著录项

  • 作者

    Chen, Pen-Chung.;

  • 作者单位

    University of Michigan.;

  • 授予单位 University of Michigan.;
  • 学科 Health Sciences Pharmacy.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 93 p.
  • 总页数 93
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药剂学;
  • 关键词

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