Thalidomide's reported ability to inhibit
tumor angiogenesis has led to clinical trials determining its effectiveness in combating various types of
cancer. Since
thalidomide exhibits low oral bioavailability due to limitations in solubility, inclusion complexation using sulfobutyl ether-7
beta-cyclodextrin was used to improve the delivery of
thalidomide. Our main goals were to increase the solubility, bioavailability as well as chemical stability of
thalidomide through complexation with anionic
beta-cyclodextrin, to characterize the complex in solid state using differential scanning calorimetry, X-ray
powder diffractometry, and to explore
thalidomide's antitumorigenic and antiangiogenesis potential when administered orally as free and in combination with
cyclodextrin to experimental animals. The aqueous solubility and aqueous alkaline stability of
thalidomide was markedly increased by the SBE7betaCD complexation.
Thalidomide administered orally in combination with SBE7betaCD, led to a significant delay in
tumor formation as a result of improved cellular
drug absorption, distribution through solubilization in experimental animals. The improved pharmacological efficacy of the
thalidomide-
cyclodextrin complex compared to free
thalidomide in mouse
melanoma model suggest that such a delivery system may be useful for the improved
therapeutics of
thalidomide, in vivo.