Shapiro Rachel L, Bethiana Titania, Carter Davell M, Ortiz Jairo, DeLong Kevin, Anders Nicole, Numan Tricia A, Duggan Eliza, Zierden Hannah C, Ensign Laura M
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA.
The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Drug Deliv Transl Res. 2025 Feb;15(2):609-620. doi: 10.1007/s13346-024-01618-6. Epub 2024 May 15.
Vaginal atrophy affects up to 57% of post-menopausal women, with symptoms ranging from vaginal burning to dysuria. Estradiol hormone replacement therapy may be prescribed to alleviate these symptoms, though many vaginal products have drawbacks including increased discharge and local tissue toxicity due to their hypertonic nature. Here, we describe the development and characterization of a Pluronic F127-coated estradiol nanosuspension (NS) formulation for improved vaginal estradiol delivery. We compare the pharmacokinetics to the clinical comparator vaginal cream (Estrace) and demonstrate increased delivery of estradiol to the vaginal tissue. We utilized ovariectomized (OVX) mice as a murine model of post-menopausal vaginal atrophy and demonstrated equivalent efficacy in vaginal re-epithelialization when dosed with either the estradiol NS or Estrace cream. Further, we demonstrate compatibility of the estradiol NS with vaginal bacteria in vitro. We demonstrate that a Pluronic F127-coated estradiol NS may be a viable option for the treatment of post-menopausal vaginal atrophy.
阴道萎缩影响多达57%的绝经后女性，症状从阴道烧灼感到排尿困难不等。可能会开雌二醇激素替代疗法来缓解这些症状，不过许多阴道用药存在缺点，包括因其高渗性质导致分泌物增多和局部组织毒性。在此，我们描述了一种用于改善阴道雌二醇递送的普朗尼克F127包被的雌二醇纳米混悬液（NS）制剂的研发与特性。我们将其药代动力学与临床对照阴道乳膏（雌二醇乳膏）进行比较，并证明雌二醇向阴道组织的递送增加。我们利用去卵巢（OVX）小鼠作为绝经后阴道萎缩的小鼠模型，并证明用雌二醇NS或雌二醇乳膏给药时，在阴道再上皮化方面具有同等疗效。此外，我们证明了雌二醇NS在体外与阴道细菌的相容性。我们证明，普朗尼克F127包被的雌二醇NS可能是治疗绝经后阴道萎缩的一个可行选择。
