Characterization of micellar systems produced by new amphiphilic conjugates of poly(ethylene glycol).

This study proposes polymeric micelles produced using new amphiphilic conjugates between amino- or carboxy-mPEG2000 and three different α-lipoamino acids (PEG-LAA). The characterization of these colloidal systems showed CMC values, in the order of 10(-5 )M, that are interesting in the view of an in vivo administration. The PEG-LAA micelles also showed a good stability at 37 °C and upon dilution in aqueous media. Using a colored probe as a model lipophilic compound, the loading efficiency and in vitro release profile were also outlined.

Lipoamino acid prodrugs of paclitaxel: synthesis and cytotoxicity evaluation on human anaplastic thyroid carcinoma cells.

Lipophilic derivatives of the anticancer drug paclitaxel (PTX) were prepared by means of its conjugation to lipoamino acid (LAA) residues, with the aim of increasing drug accumulation in tumor cells. PTX was linked to the methyl esters of norleucine (C6) or 2-aminodecanoic acid (C10). A succinic acid group was used as a spacer to link the 2'-hydroxyl group of PTX and the LAA residue, respectively by means of an ester and an amide bond. The in vitro anticancer activity of the prodrugs was tested on a human thyroid anaplastic cancer cell line (ARO). The intracellular uptake kinetics of free PTX and its prodrugs was assessed by HPLC. PTX-LAA prodrugs showed a noticeable cytotoxic activity against ARO cells at shorter incubation time (12 h) and lower doses (0.01-0.1 microM) than PTX. Intracellular accumulation experiments indicated an improvement of drug concentration inside these cells, related to the block of the cellular expulsion by means of multi drug resistance efflux complex and improved physicochemical features that allowed the greater passive cellular membrane permeation. The enhanced activity of PTX-LAA prodrugs, in terms of potency and onset of the effect, as well as the interesting intracellular accumulation data suggest that these compounds can be further tested as possible alternatives to PTX for the treatment of resistant cancer cells.