Hybrid-modified poly(D,L-lactide-co-glycolide) nanospheres for a novel cellular drug delivery system

Int J Pharm. 2010 Jun 15;392(1-2):311-3. doi: 10.1016/j.ijpharm.2010.03.042. Epub 2010 Mar 25.

Abstract

We prepared surface-modified poly(D,L-lactide-co-glycolide) (PLGA) nanospheres (NS) for use as cellular drug and gene delivery systems using an emulsion solvent diffusion method. In this study, we screened for an appropriate surface modifier to improve NS cellular uptake. Poly-L-lysine (PLL)-modified PLGA NS were taken up by A549 cells in significantly higher amounts (17-fold) than unmodified NS. In order to provide a novel function, PLGA NS were hybrid-modified using both; a cationic polymer, PLL, and a nonionic surfactant, polysorbate 80, to improve cellular uptake in serum-containing medium (SCM). Hybrid modification abrogated the decreased PLGA NS cellular uptake in SCM as a result of better dispersion in serum compared to PLL-PLGA NS, which aggregated in SCM. Luciferase activity of Hybrid-NS/pCMV-Luc complexes in A549 cells in SCM was 122-fold higher than PLL-NS. Hybrid-PLGA NS were not cytotoxic for A549 cells. In conclusion, Hybrid-PLGA NS have great potential as effective cellular drug delivery carriers.

MeSH terms

  • Biocompatible Materials / chemistry*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival
  • Chitosan / chemistry
  • DNA / administration & dosage
  • DNA / genetics
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Gene Transfer Techniques
  • Humans
  • Lactic Acid / chemistry*
  • Luciferases / genetics
  • Nanospheres / chemistry*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polylysine / chemistry
  • Polysorbates / chemistry
  • Surface Properties

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Polysorbates
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polylysine
  • Polyglycolic Acid
  • Lactic Acid
  • DNA
  • Chitosan
  • Luciferases