Abstract
Combined chemotherapy is an effective and safe treatment for cancers. Co-administration of cisplatin and gemcitabine produces a synergistic effect for bladder cancer treatment, so viscous microemulsions were developed for co-delivery of cisplatin and gemcitabine to extend the retention time and improve the permeability of chemotherapeutic drugs into the urothelium by intravesical administration. Results showed that the deposition amounts of cisplatin and gemcitabine significantly increased in in vitro and in vivo study. The penetration depth in bladder tissue samples increased from 60 to 120 μm. The dual-loaded formulation also showed thermodynamic and chemical stability, demonstrating that these gel-based microemulsions are promising drug delivery carriers for chemotherapy agents by intravesical administration.
Highlights
Cisplatin (Pt(NH3)2Cl2, MW 301.1, log P −2.19, pka 5.1, and solubility 2.53 mg/mL) is a well-known chemotherapeutic agent used for the treatment of numerous cancers including bladder, lung, ovarian, and testicular cancers
Gemcitabine hydrochloride was purchased from Scinopharm (Tainan, Taiwan), cisplatin, acetaminophen, paraformaldehyde carbamic acid ethyl ester, nickel chloride, methylcellulose, chloral hydrate, and rhodamine B from Sigma-Aldrich
The mean droplet sizes of the prepared gemcitabine-loaded microemulsions without methylcellulose ranged from 9.47 to 26.73 nm, and the polydispersity index (PDI) ranged from 0.06 to 0.30, indicating that nanoscale droplet sizes with relative monodispersing colloids were obtained from the following formulations 1 to 4 (Table 2)
Summary
Cisplatin (Pt(NH3)2Cl2, MW 301.1, log P −2.19, pka 5.1, and solubility 2.53 mg/mL) is a well-known chemotherapeutic agent used for the treatment of numerous cancers including bladder, lung, ovarian, and testicular cancers. In cells, it crosslinks with the purine bases on DNA, thereby interfering with DNA repair mechanisms, resulting in DNA damage, and induces apoptosis [1]. Gemcitabine hydrochloride (C9H11F2N3O4, MW 263.2, logP −1.4, pka 3.6, and water solubility of 51.3 mg/mL) is a chemotherapy medication used to treat a number of types of cancer including bladder cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and breast cancer [5]. Numerous studies have shown that the combination of cisplatin and gemcitabine yields a synergistic anti-tumor effect—in particular, with a ratio of 1/10~1/16, exhibiting better performance [3,8,9,10,11]
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