Abstract:
:The process of molecular self-assembly plays a crucial role in formulation of polymeric nanoparticulated drug delivery carriers as it creates the possibility for enhanced drug encapsulation and carrier surface engineering. 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(ɛ-caprolactone)-poly(acrylic acid) (PAA(13)-PCL(35)-PAA(13)) 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 × 2(2) 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 fragmented DNA in cells treated with loaded micelles compared to SN-38 solution. Altogether, these results point out to potential biomedical and clinical application of PAA-PCL-PAA systems in the future.
journal_name
J Biomater Appljournal_title
Journal of biomaterials applicationsauthors
Djurdjic B,Dimchevska S,Geskovski N,Petrusevska M,Gancheva V,Georgiev G,Petrov P,Goracinova Kdoi
10.1177/0885328214549612subject
Has Abstractpub_date
2015-01-01 00:00:00pages
867-81issue
6eissn
0885-3282issn
1530-8022pii
0885328214549612journal_volume
29pub_type
杂志文章abstract::The surface quality of coronary stents has a significant influence on its biocompatibility. Therefore, surface polishing is of paramount importance in the production and application of stents. In the present study, electropolishing is performed on 316LVM steel slotted tube coronary stents. Additionally, acid pickling,...
journal_title:Journal of biomaterials applications
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journal_title:Journal of biomaterials applications
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