Abstract
Hyaluronic acid/mannitol (HA/MN)-based par-ticles were designed as mitomycin c (MMC) delivery vehicles through the crosslinking of 1:0, 3:1, 1:3, and 0:1 mole ratios of HA/MN to investigate their potential use in bladder cancer therapy. The HA/MN-MMC particles prepared by the micro -emulsion crosslinking method were of 0.5???10 ??m size with a zeta potential value of ???36.7 mV. The MMC carrier potential of the HA/MN-MMC particles was investigated by changing HA/MN ratios in the particle structure. The MMC loading capacity of neat HA particles was 5.3 ?? 1.1 mg/g, whereas HA/MN (1:3) particles could be loaded with about three times more drug, for example, 18.4 ?? 0.8 mg/g. The kinetic of MMC drug delivery from the HA/MN-MMC particles were tested in vitro in bladder cancer conditions for example, pH 4.5, 6, and 7.4. The HA-MMC particles released approximately 70% of the loaded drug in 300 h, while 43% of the loaded drug was released from the HA/MN-MMC particles within 600 h under physiological conditions, pH 7.4, 37 ??C. The cytotoxicity of HA-based particles on healthy L929 fibroblast cells and HTB-9 human bladder cancer cells was investigated in vitro via MTT tests. Bare MMC inhibited about 90% of L929 fibroblast cells even at 100 ??g/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ?? 5 and 109 ?? 7% at 1000 ??g/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 ??g/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 ??g/mL destroyed almost all the cancer cells with 8 ?? 5% cell viability in 72 h of incubation time. The designed HA/MN-MMC (1:3) particles were found to afford a chemotherapeutic effect on the tumor cancers while reducing the toxicity of MMC against L929 fibroblast cells.
