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Carboplatin-loaded surface modified-PLGA nanoparticles confer sustained inhibitory effect against retinoblastoma cell
Hua Zhuang1,2, Ya-Nan Xu3,4, Hong-Hua Zheng3,4
1Xianyou Maternity and Childcare Hospital, Putian, 351200, Fujian Province, China.
Purpose:
To investigate the antiproliferative effect of carboplatin-loaded surface-modified poly(lactide-co-glycolide) on retinoblastoma cells.
Methods:
Carboplatin-loaded poly(lactide-co-glycolide) with or without sodium alginate surface modification was prepared using sodium alginate-poly(lactide-co-glycolide) and poly(lactide-co-glycolide). The zeta potential and carboplatin release behavior were investigated. The cellular uptake of the released drug was observed in the retinoblastoma cell line Y79. The inhibitory effect of carboplatin-loaded nanoparticles against the Y79 cell line was evaluated using methyl thiazolyl tetrazolium assay and western blot. Native carboplatin and void nanoparticles without carboplatin loading were used as controls.
Results:
The zeta potential was -(26.1 ± 3.1) mV for carboplatin-loaded poly(lactide-co-glycolide) and-(43.1 ± 8.1) mV for carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). The burst release percentages of carboplatin-loaded poly(lactide-co-glycolide) and sodium alginate-poly(lactide-co-glycolide) were (40.0% ± 8.2%) and (18.9% ± 4.3%) at 24 hours, respectively. A significant difference was identified regarding drug release between carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) and carboplatin-loaded poly(lactide-co-glycolide). Fluorescence detection revealed that intense uptake of carboplatin into the cytoplasm of the Y79 cell line that was exposed to carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). Carboplatin-loaded poly(lactide-co-glycolide) or sodium alginate-poly(lactide-co-glycolide) exposure inhibited proliferating cell nuclear antigen expression in Y79 cells on day 3. Extension of exposure to day 5 revealed that the sodium alginate-poly(lactide-co-glycolide) surface modification was superior to that of poly(lactide-co-glycolide) in terms of proliferating cell nuclear antigen inhibition. The cell viability test using methyl thiazolyl tetrazolium revealed a similar inhibitory effect. Furthermore, the carboplatin-loaded nanoparticles of lower concentration inhibited cell viability more strongly than native carboplatin of higher concentration in methyl thiazolyl tetrazolium assay.
Conclusions:
Carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) inhibited retinoblastoma cell proliferation with superior effect as compared with poly(lactide-co-glycolide) and native carboplatin. Sodium alginate surface modification offers a potential strategy for the sustained carboplatin release system.
