Evaluation of thermoresponsive properties and biocompatibility of polybenzofulvene aggregates for leuprolide delivery

Int J Pharm. 2012 Nov 15;438(1-2):279-86. doi: 10.1016/j.ijpharm.2012.09.023. Epub 2012 Sep 16.

Abstract

In this study, a polybenzofulvene derivative named poly-6-MOEG-9-BF3k, was evaluated as polymeric material for the production of injectable thermoresponsive nano-aggregates able to load low molecular weight peptidic drug, like the anticancer leuprolide. Thermoresponsive behavior of poly-6-MOEG-9-BF3k was studied in aqueous media by evaluating scattering intensity variations by means of DLS in function of temperature. Zeta potential measurements and SEM observations were also carried out. Moreover, critical aggregation temperature of the poly-6-MOEG-9-BF3k polymer was evaluated by pyrene fluorescence analysis. Then, the ability of prepared thermoresponsive aggregates to protect this model oligopeptide drug and regulate its release rate in function of external temperature was evaluated in vitro. Finally, biocompatibility of poly-6-MOEG-9-BF3k aggregates was tested in vitro on a healthy cell line (human bronchial epithelial cell; 16-HBE) and in vivo on rat animal model upon subcutaneous administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / chemistry
  • Cell Line
  • Cell Survival / drug effects
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Humans
  • Indenes / administration & dosage*
  • Indenes / chemistry
  • Leuprolide / administration & dosage*
  • Leuprolide / chemistry
  • Male
  • Microscopy, Electron, Scanning
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry
  • Nanostructures / ultrastructure
  • Polymers / administration & dosage*
  • Polymers / chemistry
  • Rats
  • Rats, Wistar
  • Skin / anatomy & histology
  • Skin / drug effects
  • Temperature

Substances

  • Antineoplastic Agents, Hormonal
  • Drug Carriers
  • Indenes
  • Polymers
  • poly-6-MOEG-9-BF3k
  • Leuprolide