Nontoxic Natural Polymeric Particle Vehicles Derived from Hyaluronic Acid and Mannitol as Mitomycin C Carriers for Bladder Cancer Treatment

ŞAHİNER N., Ayyala R. S., SUNER S. C.

ACS Applied Bio Materials, vol.5, no.12, pp.5554-5566, 2022 (ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 5 Issue: 12
  • Publication Date: 2022
  • Doi Number: 10.1021/acsabm.2c00558
  • Journal Name: ACS Applied Bio Materials
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus, BIOSIS, Compendex, MEDLINE
  • Page Numbers: pp.5554-5566
  • Keywords: biocompatible cancer treatment, bladder cancer therapy, hyaluronic acid particles, mannitol particles, mitomycin C (MMC)
  • Çanakkale Onsekiz Mart University Affiliated: Yes


© 2022 American Chemical Society.Hyaluronic acid/mannitol (HA/MN)-based particles 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 microemulsion crosslinking method were of 0.5-10 μm 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 μg/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ± 5 and 109 ± 7% at 1000 μg/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 μg/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 μg/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.