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Design and in vitro development of resorbable urologic drug delivery device

机译：可再吸收的泌尿外科给药装置的设计和体外开发

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Implantable, controlled release drug delivery devices offer several advantages over systemic oral administration routes and immediate drug release treatments including direct therapy to target organ, more continuous maintenance of plasma and tissue drug levels and the potential for reduced side effects or toxicity. Urology has emerged as a unique field in which minimally invasive implantation techniques are available and such devices could provide improved beneficial therapies over conventional treatments. Urological indications for which localized drug therapy is already being advocated and investigated are highly suitable for treatment with implantable controlled release devices. This thesis describes the in vitro performance evaluation of an implantable, bio-resorbable device that can provide localized drug therapy of ciprofloxacin (CIP) to the seminal vesicle and nearby prostate gland for treatment of chronic prostatitis (CP). The device functions as an elementary osmotic pump (EOP) to release CIP for a period of 2-3 weeks after implantation in the seminal vesicle (SV) through transrectal needle injection or cystoscopic methods. The device is composed of an elastomeric, resorbable polymer cast in a tubular geometry with solid drug powder packed into its core and a micromachined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice size in which osmotic-controlled zero-order release was the dominant mechanism of drug delivery from the device. Device stability and function in an alkaline environment of similar pH to that of the SVs and infected prostate gland was also assessed in vitro. The device was found to function well in both de-ionized water and NaOH pH-8 solution with a sustained zero-order release rate of 2.47 ± 0.29 jtg/hr when fabricated with an orifice of diameter 100-150pm.
机译：与全身口服给药途径和即时药物释放治疗相比，可植入​​的控释药物释放装置具有多个优势，包括直接治疗靶器官，更连续地维持血浆和组织药物水平以及减少副作用或毒性的潜力。泌尿外科已经成为一种独特的领域，在其中可以使用微创植入技术，并且这种设备可以提供比常规治疗更好的有益疗法。已经提倡和研究局部药物治疗的泌尿外科适应症非常适合使用植入式控释装置进行治疗。本论文描述了一种可植入生物可吸收装置的体外性能评估，该装置可为精囊和附近前列腺提供环丙沙星（CIP）的局部药物治疗，以治疗慢性前列腺炎（CP）。该设备用作基本渗透泵（EOP），可通过经直肠针头注射或膀胱镜检查方法将其植入精囊（SV）后释放CIP，持续2-3周。该装置由浇铸成管状几何形状的弹性体，可吸收的聚合物组成，其中固体药物粉末填充到其芯中，并且微机械释放孔钻穿其壁。进行了药物释放实验，以确定从单个孔口释放的有效速率以及孔口大小的范围，在该范围内，渗透控制的零级释放是从设备中释放药物的主要机制。在体外，还评估了在与SVs和感染的前列腺类似的pH值的碱性环境中的设备稳定性和功能。发现该设备在制造直径为100-150pm的孔口时，在去离子水和NaOH pH-8溶液中均能很好地工作，并且零阶持续释放速率为2.47±0.29 jtg / hr。

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