title: The use of surfactants to enhance the solubility and stability of the water-insoluble anticancer drug SN38 into liquid crystalline phase nanoparticles.
abstract: Cubosomes were used to increase the aqueous solubility of the water insoluble anticancer drug SN38. The results showed that the use of a common cubosome formulation consisting of phytantriol (PHYT) as the matrix amphiphile (PHYT-cubosome) led to a 6-fold increase in the solubility of SN38. However, mean hydrodynamic diameter (DH) and polydispersity index (PDI) of these PHYT-cubosome particles were 345±49nm and 0.37±0.05, respectively, making them unsuitable for intravenous applications. Several additives were investigated to increase the solubility of SN38 and reduce the DHand PDI values of the resulting particles. Charged additives such as didodecyldimethyl ammonium bromide (DDAB) and sodium dodecyl sulfate (SDS) led to improvements in the physiochemical properties of the cubosomes. Notably, the PHYT-DDAB and PHT-SDS cubosomes led to 15- and 14-fold increases in the aqueous solubility of SN38, respectively. Moreover, the SN38 loaded into the PHYT-DDAB and PHYT-SDS cubosomes was found to be highly stable, with very little hydrolysis to its inactive acid form. In summary, the addition of DDAB and SDS to PHYT-cubosome nanoparticle drug delivery systems not only led to considerable improvements in their physiochemical properties, but also enhanced the aqueous solubility of SN38 and increased its chemical stability.
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Abdul-Hackam
authors: AH
authors: Ranneh
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Yasunori
authors: Y
authors: Iwao
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Shuji
authors: S
authors: Noguchi
authors: Department of Physics, Graduate School of Science, Shizuoka University; 836 Oya, Suruga-ku, Shizuoka 422-8529, Japan.
authors: Toshihiko
authors: T
authors: Oka
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: s-itai@u-shizuoka-ken.ac.jp.
authors: Shigeru
authors: S
authors: Itai
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001965:Bromides / Q000737:chemistry; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D000077146:Irinotecan; D050866:Liquid Crystals / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001965:Bromides; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; D014867:Water; D012967:Sodium Dodecyl Sulfate; D000077146:Irinotecan; C051470:ammonium bromide; D002166:Camptothecin
keywords: Chemical stability; Cubosomes; Hydrolysis; Poorly water-soluble drug; SN38