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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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Smejkalová D,Nešporová K,Hermannová M,Huerta-Angeles G,Cožíková D,Vištejnová L,Safránková B,Novotný J,Kučerík J,Velebný V

doi

10.1016/j.ijpharm.2014.03.024

subject

Has Abstract

pub_date

2014-05-15 00:00:00

pages

147-55

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(14)00167-7

journal_volume

466

pub_type

杂志文章

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