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Paclitaxel isomerisation in polymeric micelles based on hydrophobized hyaluronic acid.

Abstract
Physical and chemical structure of paclitaxel (PTX) was studied after its incorporation into polymeric micelles made of hyaluronic acid (HA) (Mw=15 kDa) grafted with C6 or C18:1 acyl chains. PTX was physically incorporated into the micellar core by solvent evaporation technique. Maximum loading capacity for HAC6 and HAC18:1 was determined to be 2 and 14 wt.%, respectively. The loading efficiency was higher for HAC18:1 and reached 70%. Independently of the derivative, loaded HA micelles had spherical size of approximately 60-80 nm and demonstrated slow and sustained release of PTX in vitro. PTX largely changed its form from crystalline to amorphous after its incorporation into the micelle's interior. This transformation increased PTX sensitivity towards stressing conditions, mainly to UV light exposure, during which the structure of amorphous PTX isomerized and formed C3C11 bond within its structure. In vitro cytotoxicity assay revealed that polymeric micelles loaded with PTX isomer had higher cytotoxic effect to normal human dermal fibroblasts (NHDF) and human colon carcinoma cells (HCT-116) than the same micelles loaded with non-isomerized PTX. Further observation indicated that PTX isomer influenced in different ways cell morphology and markers of cell cycle. Taken together, PTX isomer loaded in nanocarrier systems may have improved anticancer activity in vivo than pure PTX.
AuthorsDaniela Smejkalová, Kristina Nešporová, Martina Hermannová, Gloria Huerta-Angeles, Dagmar Cožíková, Lucie Vištejnová, Barbora Safránková, Jaroslav Novotný, Jiří Kučerík, Vladimír Velebný
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 466 Issue 1-2 Pg. 147-55 (May 15 2014) ISSN: 1873-3476 [Electronic] Netherlands
PMID24614580 (Publication Type: Journal Article)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Micelles
  • Polymers
  • Hyaluronic Acid
  • Paclitaxel
Topics
  • Antineoplastic Agents, Phytogenic (administration & dosage, chemistry)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Drug Carriers (administration & dosage, chemistry)
  • Fibroblasts (drug effects)
  • HCT116 Cells
  • Humans
  • Hyaluronic Acid (administration & dosage, chemistry)
  • Hydrophobic and Hydrophilic Interactions
  • Isomerism
  • Micelles
  • Paclitaxel (administration & dosage, chemistry)
  • Polymers (administration & dosage, chemistry)

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