Sunflower pollen microcapsules as drug carriers for bladder perfusion chemotherapy of bladder cancer
Objective To investigate the safety as well as efficacy of sunflower pollen microcap-sules as drug carriers for bladder instillation.Methods Natural sunflower pollen was defatted,hollowed out and coated with alginate to finally prepare sunflower pollen microcapsules,and the morphological char-acteristics of the pollen were observed using scanning electron microscopy.In the in vitro experiments,mouse bladder cancer MB49 cells were divided into pollen co-culture and control groups,and cell viability was determined using the cell counting kit-8(CCK-8)assay,and changes in cytokines secreted by the cells were detected using enzyme linked immunosorbent assay(ELISA).The slow release effect of pollen micro-capsules was tested using fluoresceine isothiocyanate-bovine serum albumin(FITC-BSA)as a simulated drug loading into pollen.For in vivo experiments,BALB/c-Nu nude mice were used to establish in situ bladder cancer model with MB49 cells,and bladder perfusion chemotherapy with gemcitabine or pollen mi-crocapsules loaded with gemcitabine was performed to observe the therapeutic effect.All results were ex-pressed as mean±standard deviation,and one-sample t-test was used to compare the differences between the two groups.Results The results of CCK-8 assay indicated that pollen was not significantly cytotoxic to MB49 cells at different concentrations and time points(P＞0.05).ELISA assay showed that pollen micro-capsules promoted the secretion of cytokines in MB49 cells[IL-2(1.230±0.208)vs.(0.670± 0.208)pg/ml,t=3.297,P＜0.05;IL-6(2 027.00±64.29)vs.(1 550.00±70.00)pg/ml,t=8.693,P＜0.05);IL-8(26.330±1.528)vs.(22.900±1.054)ng/ml,t=3.200,P＜0.05;TNF-α(99.670±3.512)vs.(75.670±7.024)pg/ml,t=5.293,P＜0.05,P＜0.05],which was attenuated by sodium alginate coating[IL-2(0.830±0.153)vs.(1.230±0.208)pg/ml,t=3.354,P＜0.05;IL-6(1 770.00±62.45)vs.(2 027.00±64.29)pg/ml,t=4.966,P＜0.05;IL-8(27.700±1.852)vs.(26.330±1.528)ng/ml,t=0.990,P＞0.05;TNF-α(82.670±8.505)vs.(99.670±3.512)pg/ml,t=3.200,P＜0.05].The drug release profile showed that alginate coating significantly extended the drug re-lease time of sunflower pollen microcapsules(t=70.730,P＜0.05).The results of in vivo experiments confirmed that the number of bladder tumour lesions in mice was significantly less in the sunflower pollen group than the direct infusion group(2.20±0.83 vs.5.60±1.14,t=5.391,P＜0.05).Conclusion This study demonstrated that natural sunflower pollen granules have good safety and efficacy as a drug deliv-ery vehicle in bladder cancer bladder perfusion therapy,and are a promising new material in bladder perfu-sion.
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