Department of Bioengineering, University of Washington, 3720 15th Avenue Northeast, Seattle, Washington 98105, United States.
Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, United States.
ACS Biomater Sci Eng. 2022 Jul 11;8(7):2995-3009. doi: 10.1021/acsbiomaterials.2c00357. Epub 2022 Jun 24.
Medical technology that blocks the fallopian tubes nonsurgically could increase access to permanent contraception and address current unmet needs in family planning. To achieve total occlusion of the fallopian tube via scar tissue formation, acute trauma to the tubal epithelium must first occur followed by a sustained and ultimately fibrotic inflammatory response. Here, we developed drug-eluting fiber-based microparticles that provide tunable dose and release of potent sclerosing agents. This fabrication strategy demonstrates high encapsulation of physicochemically diverse agents and the potential for scalable manufacturing by utilizing free-surface electrospinning to generate material for fiber micronization. Manipulation of nanofiber formulation such as drug loading, drug hydrophobicity, polymer hydrophobicity, and crystallinity allowed for modulation of the sustained release properties of our fiber microparticles. We assessed various fibrous microparticle formulations using a newly developed and validated guinea pig model for contraception. We found that fiber microparticles with bolus release doxycycline effectively elicited acute trauma and those formulated with highly loaded phenyl benzoate caused sustained inflammation in the target organs. The demonstrated potency of these electrospun microparticles, as well as their embolic size and shape, suggests potential for proximal agglomeration and inflammatory activity in the fallopian tubes following transcervical delivery.
非手术性阻断输卵管的医疗技术可以增加永久性避孕的可及性，并满足当前计划生育领域的未满足需求。为了通过疤痕组织形成实现输卵管的完全闭塞，输卵管上皮必须首先发生急性创伤，然后是持续的、最终纤维化的炎症反应。在这里，我们开发了基于载药纤维的微颗粒，提供了可调节的药物剂量和释放强效的硬化剂。这种制造策略展示了高封装物理化学性质不同的药物，并通过利用自由表面静电纺丝来生成纤维微细化材料，展示了大规模制造的潜力。通过对纳米纤维配方（如药物负载、药物疏水性、聚合物疏水性和结晶度）进行操作，可以调节我们纤维微颗粒的持续释放特性。我们使用新开发和验证的避孕豚鼠模型评估了各种纤维微颗粒配方。我们发现，具有推注式释放强力霉素的纤维微颗粒有效地引起了急性创伤，而那些用高负载苯佐卡因制成的纤维微颗粒则在靶器官中引起了持续的炎症。这些静电纺丝微颗粒的显示出的效力，以及它们的栓塞大小和形状，表明在经宫颈递送至输卵管后，它们有可能在输卵管近端聚集和引发炎症反应。
