Preparation of emulsions-filled sodium alginate hydrogel beads to enhance the anti-cancer activity of fangchinoline in vivo and in vitro.

[Display omitted] • Fan@EM-HGB were designed and prepared using spontaneous emulsification and ionic cross-linking. • The released behavior of Fan@EM-HGB followed a pH-controlled mechanism. • Fan@EM-HGB promote the apoptosis of A549 cells in vitro. • Fan@EM-HGB inhibit the PI3K/Akt/mTOR signaling pathway in nude mice. • Emulsions-filled hydrogel beads could be considered as a potential carrier to delivery hydrophobic active composition. Fangchinoline (Fan) is a natural alkaloids compound with a series of remarkable bioactivity, but the poor aqueous solubility limits the clinical application. Emulsions (EM) systems are commonly used to encapsulate and deliver hydrophobic active compound to enhance the bioavailability. Hydrogel beads (HGB) are three-dimensional hydrophilic polymer networks, which are able to immobilize colloidal delivery systems, resulting to the enhanced stability and controlled release in the gastrointestinal tract. In order to give full play to the bilateral advantages of emulsion and hydrogel, Fan loaded EM-filled sodium alginate HGB (Fan@EM-HGB) were designed and prepared in this paper. The average size of Fan@EM was 121.6 ± 2.7 nm and the zeta potential was -17.7 ± 0.3 mV. Physicochemical characterization demonstrated that Fan was successfully encapsulated in HGB with entrapment efficiency of 93.98 % and drug loading of 5.18 mg/g. The released behavior of Fan@EM-HGB followed a pH-controlled mechanism that was consistent with the first-order model. In vitro activity research shown that Fan@EM-HGB could significantly promote the apoptosis of A549 cells, with IC 50 value more than 2.37 times higher than that of Fan. The in vivo results indicated that Fan@EM-HGB had an obvious anti- cancer effect, and molecular mechanism shown that Fan@EM-HGB could promote tumor cell apoptosis by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway. The above research results suggest that nanoemulsions-filled hydrogel beads have potential application in delivery system for hydrophobic composition. [ABSTRACT FROM AUTHOR]