Patki Manali, Giusto Kiersten, Gorasiya Samir, Reznik Sandra E, Patel Ketan
Pharmaceutical Sciences, St. John's University, Queens, NY 11439, USA.
Pathology and Obstetrics and Gynecology and Women's Health, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Pharmaceutics. 2019 Jul 14;11(7):335. doi: 10.3390/pharmaceutics11070335.
Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena-once-a-week intramuscular injection of 17-α Hydroxyprogesterone caproate (17P)-is the only FDA approved treatment for the prevention of PTB. Invasive delivery of 17P requires hospitalization and expert personnel for injection. Vaginal delivery of 17P would be preferable, because of high patient compliance, reduced systemic exposure, fewer side effects, and no need for hospitalization. The objective of the present study was to prepare and evaluate a self-nanoemulsifying vaginal tablet of 17P. A solid self-nanoemulsifying preconcentrate (S-SNEDDS) of 17P and dimethylacetamide (DMA) was developed using medium chain triglycerides, a non- immunogenic surfactant, and co-processed excipient (PVA-F100). The tablet prepared was characterized for emulsification time, particle size, solid state properties, and drug release. The formulation showed >50% inhibition of TNF-α release from LPS-stimulated RAW 264.7 cells. Importantly, there were significant differences in rates of PTB and average time to delivery between control and vaginal 17P-treated groups in LPS-stimulated timed pregnant E15.5 mice. Considering the lacuna of therapeutic approaches in this area, vaginal delivery of 17P for the prevention of preterm birth has significant clinical relevance.
早产（PTB）是美国乃至全球婴儿死亡的主要原因。Makena（每周一次肌肉注射己酸17-α羟孕酮（17P））是美国食品药品监督管理局（FDA）批准的唯一用于预防早产的治疗方法。17P的侵入性给药需要住院治疗，并由专业人员进行注射。17P的阴道给药可能更可取，因为患者依从性高、全身暴露减少、副作用更少且无需住院。本研究的目的是制备并评估17P的自纳米乳化阴道片。使用中链甘油三酯、一种非免疫原性表面活性剂和共处理辅料（聚乙烯醇-F100）开发了17P和二甲基乙酰胺（DMA）的固体自纳米乳化预浓缩物（S-SNEDDS）。对制备的片剂进行了乳化时间、粒径、固态性质和药物释放方面的表征。该制剂对脂多糖刺激的RAW 264.7细胞中TNF-α释放的抑制率>50%。重要的是，在脂多糖刺激的孕15.5天定时怀孕小鼠中，对照组和阴道给予17P治疗组之间的早产率和平均分娩时间存在显著差异。考虑到该领域治疗方法的空白，17P阴道给药预防早产具有重要的临床意义。
