Shape-Memory Terpolymer Rods with 17-β-estradiol for the Treatment of Neurodegenerative Diseases: an In Vitro and In Vivo Study

Pharm Res. 2016 Dec;33(12):2967-2978. doi: 10.1007/s11095-016-2019-9. Epub 2016 Sep 14.

Abstract

Purpose: Estradiol (E2)-loaded poly(L-lactide-co-glycolide-trimethylenecarbonate) (P(L-LA:GA:TMC)) rods with shape-memory were developed for the treatment of neurodegenerative diseases. Usefulness of the extrusion method in the obtaining process was also considered. The influence of structural and surface properties during hydrolytic degradation was developed. The possible therapeutic aspect of rods with E2 was determined.

Methods: The extruded rods were incubated in a PBS solution (pH 7.4, 37°C, 240 rpm). The amount of released E2 in vitro conditions was estimated by UV-VIS method. The following methods in the degradation of rods were applied: NMR, DSC, FTIR, GPC, SEM, and optical microscopy. Changes in water uptake and weight loss were also determined. In vivo study was performed on rats. Measurements of E2 level were performed before and after ovariectomy of rats using ELISA method. A sample of tissue adjacent to the site of the rod implantation was analysed under an optical microscope.

Results: A stable and steady degradation process ensured zero-order release of E2. The in vivo study indicated a significant increase in the E2 level in serum after ovariectomy. Moreover, structural and surface features indicated that the extrusion method was appropriate for obtaining E2-loaded rods.

Conclusions: Shape-memory P(L-LA:GA:TMC) rods with E2 are an adequate proposal for further research in the field of neurological disorders.

Keywords: 17-β-estradiol; degradation; poly(L-lactide-co-glycolide-trimethylenecarbonate); rods; zero-order release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Drug Liberation
  • Estradiol / administration & dosage*
  • Estradiol / chemistry
  • Estradiol / pharmacokinetics
  • Female
  • Hydrolysis
  • Nanotubes / chemistry*
  • Neurodegenerative Diseases / drug therapy*
  • Polyesters / chemistry*
  • Rats, Wistar
  • Surface Properties
  • Tissue Distribution

Substances

  • Polyesters
  • poly(L-lactide-co-glycolide-trimethylenecarbonate)
  • Estradiol