title: Thermosensitive progesterone hydrogel: a safe and effective new formulation for vaginal application.
abstract: OBJECTIVE
  The safe and functional delivery of progesterone through the vaginal route remains an unmet clinical need. The purpose of this work is to prepare a new progesterone (P4) gel for vaginal application using a thermosensitive mucoadhesive polymer, glycol chitin (GC).
  
  
  METHODS
  Thermogelling, mucoadhesive, mechanical, and viscoelastic properties of GC and the new formulation were evaluated using rheometry. In vitro release profile and the bioactivity of P4 were determined using vaginal fluid simulant (VFS) pH 4.2, and PR-reporter gene assay, respectively. In vitro safety of the formulations was tested using (VK2/E6E7) vaginal epithelial cell line and Lactobacillus Crispatus. Finally, in vivo safety and the efficacy of this formulation were evaluated using an endometrial hypoplasia mouse model.
  
  
  RESULTS
  Results shows the aqueous solution of 5%; (w/v) GC loaded with 0.1%; (w/v) P4 prepared in pH 4.2, (GC-P4), forms a thermosensitive mucoadhesive hydrogel and can maintain stable physical properties at 37 °C. GC-P4 gel release 50% of P4 in 4 h after exposure to VFS, and no significant decrease in % viability of VK2/E6E7 or Lactobacillus was found after exposure to 5% GC or GC-P4. GC-P4 does not exhibit obvious toxicities to vaginal tissue in vivo even after repeated application. Efficacy studies indicated that GC-P4 was capable of preventing the progression of simple endometrial hyperplasia (SEH) to complex atypical endometrial hyperplasia (CAEH) in vivo.
  
  
  CONCLUSIONS
  Results indicates that GC-P4 retains many characteristics for an effective vaginal delivery system for P4. Therefore we believe that GC-P4 formulation is a promising alternative to current vaginal P4 formulation.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, Utah, 84132, USA.
authors.forename: Aliyah
authors.initials: A
authors.lastname: Almomen
authors.forename: Sungpil
authors.initials: S
authors.lastname: Cho
authors.forename: Chieh-Hsiang
authors.initials: CH
authors.lastname: Yang
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Li
authors.forename: Elke A
authors.initials: EA
authors.lastname: Jarboe
authors.forename: C Matthew
authors.initials: CM
authors.lastname: Peterson
authors.forename: Kang Moo
authors.initials: KM
authors.lastname: Huh
authors.forename: Margit M
authors.initials: MM
authors.lastname: Janát-Amsbury
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004714:Endometrial Hyperplasia / Q000188:drug therapy; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007778:Lactobacillus / Q000187:drug effects; D051379:Mice; D044367:Phase Transition; D011374:Progesterone / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012212:Rheology; D013696:Temperature; D014014:Tissue Adhesives / Q000737:chemistry; D014621:Vagina / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D011980:Receptors, Progesterone; D014014:Tissue Adhesives; D002686:Chitin; D011374:Progesterone; C031610:glycolchitin