title: 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.
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic. Electronic address: daniela.smejkalova@contipro.com.
authors.forename: Daniela
authors.initials: D
authors.lastname: Smejkalová
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Kristina
authors.initials: K
authors.lastname: Nešporová
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Hermannová
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Cožíková
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Vištejnová
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Safránková
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Novotný
authors.affiliation: University of Koblenz-Landau, Campus Landau, Institute for Environmental Sciences, Fortstraße 7, 768 29, Landau, Germany.
authors.forename: Jiří
authors.initials: J
authors.lastname: Kučerík
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007536:Isomerism; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D006820:Hyaluronic Acid; D017239:Paclitaxel
keywords: Hyaluronan; Hyaluronic acid (PubChem CID: 453617); Isomer; Paclitaxel; Paclitaxel (PubChem CID: 44155032); Polymeric micelle; Stability