Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern 3012, Switzerland.
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern 3012, Switzerland.
Eur J Pharm Sci. 2023 Sep 1;188:106501. doi: 10.1016/j.ejps.2023.106501. Epub 2023 Jun 18.
Gynaecological health is a neglected field of research that includes conditions such as endometriosis, uterine fibroids, infertility, viral and bacterial infections, and cancers. There is a clinical need to develop dosage forms for gynecological diseases that increase efficacy and reduce side effects and explore new materials with properties tailored to the vaginal mucosa and milieu. Here, we developed a 3D printed semisolid vaginal ovule containing pirfenidone, a repurposed drug candidate for endometriosis. Vaginal drug delivery allows direct targeting of the reproductive organs via the first uterine pass effect, but vaginal dosage forms can be challenging to self-administer and retain in situ for periods of more than 1-3 h. We show that a semisoft alginate-based vaginal suppository manufactured using semisolid extrusion additive manufacturing is superior to vaginal ovules made using standard excipients. The 3D-printed ovule showed a controlled release profile of pirfenidone in vitro in standard and biorelevant release tests, as well as better mucoadhesive properties ex vivo. An exposure time of 24 h of pirfenidone to a monolayer culture of an endometriotic epithelial cell line, 12Z, is necessary to reduce the cells' metabolic activity, which demonstrates the need for a sustained release formulation of pirfenidone. 3D printing allowed us to formulate mucoadhesive polymers into a semisolid ovule with controlled release of pirfenidone. This work enables further preclinical and clinical studies into vaginally administered pirfenidone to assess its efficacy as a repurposed endometriosis treatment.
妇科健康是一个被忽视的研究领域，其中包括子宫内膜异位症、子宫肌瘤、不孕、病毒和细菌感染以及癌症等病症。临床上需要开发用于妇科疾病的剂型，以提高疗效，降低副作用，并探索具有针对阴道黏膜和环境特性的新材料。在这里，我们开发了一种含有吡非尼酮的 3D 打印半固态阴道栓剂，吡非尼酮是一种用于子宫内膜异位症的药物。阴道给药可通过首过子宫效应直接靶向生殖器官，但阴道剂型可能难以自行给药，并在原位保留超过 1-3 小时。我们证明，使用半固态挤出添加剂制造的基于海藻酸钠的半软性阴道栓剂优于使用标准赋形剂制造的阴道栓剂。3D 打印的栓剂在标准和生物相关释放测试中显示出吡非尼酮的控释曲线，以及更好的体外粘膜粘附性能。将单层培养的子宫内膜异位症上皮细胞系 12Z 暴露于吡非尼酮 24 小时是必要的，以降低细胞的代谢活性，这表明需要一种持续释放的吡非尼酮制剂。3D 打印使我们能够将粘膜粘附聚合物制成具有吡非尼酮控释的半固态栓剂。这项工作为进一步进行阴道给予吡非尼酮的临床前和临床研究奠定了基础，以评估其作为一种重新利用的子宫内膜异位症治疗方法的疗效。
