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Amphiphilic hyper-branched co-polymer nanoparticles for the controlled delivery of anti-tumor agents.

Abstract
In this investigation, we have designed and synthesized an amphiphilic co-polymer with hyper-branched poly(amine-ester) and polylactide (HPAE-co-PLA) to generate nanoparticles (NPs). These have been used to encapsulate a highly active hydrophobic anti-tumor agent, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT). Encapsulation in NPs was done in an effort to increase the anti-tumor activity of this agent by facilitating its delivery to tumor cells. We have also examined and optimized the formulation parameters of the NPs that alter their drug-loading capacity and their physical, chemical and biological properties. The resulting NPs exhibited high Bp4eT-loading capacity and substantial stability in aqueous solution. In vitro drug release studies demonstrated a controlled drug release profile with increased release at acidic pH. Anti-tumor proliferation assays showed that both free drug and drug-encapsulated NPs markedly inhibited tumor cell proliferation in a time- and concentration-dependent manner. Direct microscopic observation revealed that the fluorescent NPs were taken up by cells and localized, in part, in organelles consistent with lysosomes. These results demonstrate a feasible application of the amphiphilic hyper-branched co-polymer, HPAE-co-PLA, as nanocarriers for intracellular delivery of potent anti-tumor agents.
AuthorsQinghua Miao, Dongxue Xu, Zhi Wang, Li Xu, Tiewei Wang, Yan Wu, David B Lovejoy, Danuta S Kalinowski, Des R Richardson, Guangjun Nie, Yuliang Zhao
JournalBiomaterials (Biomaterials) Vol. 31 Issue 28 Pg. 7364-75 (Oct 2010) ISSN: 1878-5905 [Electronic] Netherlands
PMID20599267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Polymers
Topics
  • Antineoplastic Agents (chemistry, metabolism, pharmacology)
  • Cell Line, Tumor (drug effects)
  • Drug Carriers (chemical synthesis, chemistry, therapeutic use)
  • Drug Compounding
  • Drug Delivery Systems (methods)
  • Humans
  • Materials Testing
  • Molecular Structure
  • Nanoparticles (chemistry)
  • Polymers (chemical synthesis, chemistry, pharmacology)

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