Novel Poly(Diol Sebacate)s as Additives to Modify Paclitaxel Release From Poly(Lactic-co-Glycolic Acid) Thin Films

J Pharm Sci. 2017 Aug;106(8):2106-2114. doi: 10.1016/j.xphs.2017.05.012. Epub 2017 May 20.

Abstract

Paclitaxel (PTX) incorporation in poly(lactic-co-glycolic acid) (PLGA) matrices produce films with high tensile rigidity and slow release that fail to deliver the required release rate for most biomedical applications such as in drug eluting stents and cancer treatments. To modify and improve this behavior, a set of poly(diol sebacate)s were synthesized and fully characterized as possible additives. The tensile properties of PLGA blends were evaluated as these materials could be used as coatings in drug eluting stent applications. A significant improvement in mechanical flexibility was observed with 20% additive content, as it reduced the Young's modulus value and increased the maximum deformation at break. PTX release was studied and correlated with the release of additive from PLGA films. An increase in the initial burst release phase was observed on all blends when compared to the control films of PLGA. Modulation of PTX release was achieved by altering the hydrophilicity degree of the additive or its percentage content on the blend. This supports the possibility that PTX was partitioned into the additive phase. Cytotoxicity analyses of novel additives were performed on mouse embryonic fibroblasts NIH/3T3.

Keywords: PLGA; coating; drug delivery systems; polymer synthesis; polymeric biomaterials.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / toxicity
  • Decanoic Acids / chemistry*
  • Decanoic Acids / toxicity
  • Dicarboxylic Acids / chemistry*
  • Dicarboxylic Acids / toxicity
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Elastic Modulus
  • Lactic Acid / chemistry*
  • Lactic Acid / toxicity
  • Mice
  • NIH 3T3 Cells
  • Paclitaxel / administration & dosage*
  • Polyglycolic Acid / chemistry*
  • Polyglycolic Acid / toxicity
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Polymers / toxicity

Substances

  • Antineoplastic Agents, Phytogenic
  • Biocompatible Materials
  • Decanoic Acids
  • Dicarboxylic Acids
  • Drug Carriers
  • Polymers
  • poly(diol sebacate)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Paclitaxel