Encapsulation and release of hydrocortisone from proliposomes govern vaginal delivery

Drug Deliv Transl Res. 2023 Apr;13(4):1022-1034. doi: 10.1007/s13346-022-01263-x. Epub 2022 Dec 30.

Abstract

Topical preparations of hydrocortisone can be used for the anti-inflammatory treatment of the female genital area. Although the drug is a low-strength corticosteroid, systemic absorption and distribution of the drug are the most common safety risks associated with this therapy. In the current investigation, we elucidate the physicochemical properties of lipid-based drug carrier systems that govern the local bioavailability of hydrocortisone for intravaginal administration. For this purpose, we compared various proliposome formulations with a commercial cream. Depending on the availability of physiological acceptors, encapsulation and drug release from the lipid phase were found to be the most important drivers of drug bioavailability. The high permeability of hydrocortisone leads to rapid transport of the drug across the mucosal cell layer as indicated by experiments using HEC-1-A and CaSki cell monolayer models. Under sink conditions, differences in the release from the liposomes as determined in the Dispersion Releaser were almost negligible. However, under non-sink conditions, the drug release plateaued at levels corresponding to the encapsulation efficiency. After redispersion, all liposomal formulations performed better than the commercial drug product indicating that the encapsulation into the lipid phase is the main driver sustaining the release.

Keywords: Drug delivery; In vitro dissolution; Liposomes; Nanocarrier; Permeability; Vesicles.

MeSH terms

  • Delivery, Obstetric
  • Drug Carriers / chemistry
  • Female
  • Humans
  • Hydrocortisone*
  • Lipids / chemistry
  • Liposomes* / chemistry
  • Particle Size
  • Pregnancy

Substances

  • Hydrocortisone
  • Liposomes
  • Drug Carriers
  • Lipids