Solubility measurement and RESOLV-assisted nanonization of gambogic acid in supercritical carbon dioxide for cancer therapy
Despite the captivating interest for its potential anticancer efficacy against multiple types of cancer and ability to overcome multidrug resistance, the practical application of gambogic acid (GA) has been hampered by its poor water solubility. Herein, the fabrication of nanosized GA particles (251.2 nm ± 85.6 nm) using eco-friendly supercritical fluid (SCF)-assisted rapid expansion of a supercritical solution into a liquid solvent (RESOLV) process was demonstrated. The equilibrium solubility of GA in supercritical carbon dioxide (SC−CO 2 ) was initially determined at altered supercritical conditions (P: 10.0 MPa to 30.0 MPa, T: 308.15 K–328.15 K) and the obtained data points were then correlated using various density-based models including Méndez-Santiago and Teja, Bartle as well as Chrastil models. The solubility of GA in SC−CO 2 was found to be between 1.63 × 10 −6 and 22.62 × 10 −6 in terms of GA mole fraction, and considerably good correlation agreement was obtained with all the applied models and being the lowest deviations obtained with the Méndez-Santiago and Teja model. Furthermore, the fabricated GA nanoparticles (NPs) through benign RESOLV technique, were systematically characterized. Subsequently, in vitro antiproliferation tests resulted in its augmented antitumor efficacy due to enhanced solubility of GA. Together, the results have suggested that the benign RESOLV process has successfully fabricated nanosuspensions of GA with enhanced bioavailability and antineoplastic efficacy and may have great potential in pharmaceutics.
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