School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States of America.
Surgical Infection Program, Department of Surgery and Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2014 Jan 7;9(1):e84360. doi: 10.1371/journal.pone.0084360. eCollection 2014.
Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca(2+) is less stable at acidic pH, enabling 'smart' drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca(2+) concentration, and Ca(2+) incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca(2+) binding affinity, enabling its use in a variety of biomedical applications.
感染和炎症是严重影响植入式医疗植入物功能和寿命的常见并发症。全身给予抗生素和抗炎药物通常无法达到有效浓度，并引发严重的副作用。从药物洗脱涂层局部递送治疗剂是一种很有前途的解决方案。然而，为了确保有足够的药物负载和持续释放，通常使用疏水性和厚涂层，这可能会限制组织整合和组织与器械的交流。本研究中开发并表征了一种钙介导的药物输送机制。这种新机制允许纳米级亲水聚电解质多层从控、持续释放米诺环素，米诺环素是一种有效的抗生素和抗炎药物，在生理相关浓度下可超过 35 天。在酸性 pH 值下，由于米诺环素与 Ca(2+) 的螯合作用不太稳定，观察到 pH 响应性米诺环素释放，从而能够响应感染和/或炎症引起的组织酸中毒进行“智能”药物输送。通过改变初始负载、Ca(2+)浓度以及将 Ca(2+)掺入不同层，可以控制米诺环素的释放动力学，从而能够轻松开发具有多种释放动力学的植入物涂层。这种药物输送平台可用于释放任何与 Ca(2+)结合亲和力高的药物，从而使其能够在多种生物医学应用中使用。
