Controlled release of injectable liposomal in situ gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits

J Liposome Res. 2016;26(2):148-55. doi: 10.3109/08982104.2015.1060612. Epub 2015 Jul 7.

Abstract

Background and objective: The aim of the present study was to develop and examine a new non-invasive injectable graft for the repair of alveolar bone clefts using recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated within injectable liposomal in situ gel (LIG).

Method: Different liposomal formulations loaded with rhBMP-2 were prepared, and the effects of the preparation methods and lipid content on the efficiency of rhBMP-2 encapsulation within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum (DGG) was used, and the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetics and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and treated with different injectable formulae, including rhBMP-2 liposomes and in situ gel (rhBMP-2-LIG).

Results: The results indicated that the prepared rhBMP-2-LIG prolonged the release and residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated using this novel formula.

Conclusion: BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities.

Keywords: Alveolar defect; bone morphogenetic proteins; cleft lip and palate; encapsulation; liposomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Process / drug effects*
  • Alveolar Process / growth & development
  • Alveolar Process / pathology
  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Cancellous Bone / drug effects*
  • Cancellous Bone / pathology
  • Cleft Palate / drug therapy*
  • Gels
  • Humans
  • Liposomes
  • Male
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Transforming Growth Factor beta / administration & dosage*
  • Transforming Growth Factor beta / therapeutic use*

Substances

  • Bone Morphogenetic Protein 2
  • Gels
  • Liposomes
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2