Gelatin Porous Scaffolds as Delivery Systems of Calcium Alendronate

Macromol Biosci. 2017 Mar;17(3). doi: 10.1002/mabi.201600272. Epub 2016 Oct 17.

Abstract

The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H2 O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H2 O content (0, 3, and 6 wt%). At variance, pore size varies with composition. The relative increase of the number of smaller pores on increasing BP content is in agreement with the parallel significant increase of the compressive modulus and collapse strength. The scaffolds exhibit a sustained CaAL•H2 O release profile, and a significant amount of the drug is retained in the scaffolds even after 14 d. In vitro tests are carried out using cocultures of osteoblast (OB) and osteoclast (OC). The evaluation of differentiation markers is performed both on the supernatants of cell culture and by means of quantitative polymerase chain reaction. The results indicate that BP containing scaffolds support osteoblast proliferation and differentiation, whereas they inhibit osteoclast viability and activity, displaying a promising beneficial role on bone repair processes.

Keywords: bisphosphonates; drug delivery systems; gelatin scaffolds; mechanical properties.

MeSH terms

  • Alginates / administration & dosage*
  • Alginates / chemistry
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Drug Delivery Systems*
  • Gelatin / administration & dosage
  • Gelatin / chemistry
  • Glucuronic Acid / administration & dosage
  • Glucuronic Acid / chemistry
  • Glutaral / administration & dosage
  • Glutaral / chemistry
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / chemistry
  • Humans
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoclasts / drug effects
  • Porosity
  • Tissue Scaffolds / chemistry

Substances

  • Alginates
  • Hexuronic Acids
  • Glucuronic Acid
  • Gelatin
  • Glutaral