Synthesis and self-assembly of amphiphilic poly(acrylicacid)-poly({varepsilon}-caprolactone)-poly(acrylicacid) block copolymer as novel carrier for 7-ethyl-10-hydroxy camptothecin

This study aimed to develop a novel self-assembled polymeric micelles for targeted delivery in tumor cells in order to overcome not only various drawbacks of 7-ethyl-10-hydroxy camptothecin (SN-38) but also various reported limitations of other drug delivery systems, especially low drug loading and premature release. Custom synthesized amphiphilic triblock copolymer poly(acrylic acid)–poly(-caprolactone)–poly(acrylic acid) (PAA13–PCL35–PAA13) was used to prepare kinetically stable micelles by nanoprecipitation and modified nanoprecipitation procedure. Core-shell micelles with diameter of 120–140 nm, negative zeta potential and satisfactory drug loading were produced. The prepared formulations were stable in pH range of 3–12 and in media with NaCl concentration <1 mol/l. Screening mixed level factorial 3 x 22 design identified that the process temperature as well as the type of organic solvent has influence upon the efficacy of encapsulation, particle size, dissolution rate and burst release. Fourier transform infrared and differential scanning calorimetry analyses confirmed the entrapment of the active substance into the micelles. The kinetic analysis of dissolution studies revealed that the main mechanism of drug release from the prepared formulations is Fickian diffusion. Growth inhibition studies as well as DNA fragmentation assay performed on SW-480 cell lines clearly demonstrated increased growth inhibition effect and presence of fr...
Source: Journal of Biomaterials Applications - Category: Materials Science Authors: Tags: Nanotechnology in Biomaterials Source Type: research