Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation.
Encapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials.
['Sayed|Elshaimaa|E|', 'Karavasili|Christina|C|', 'Ruparelia|Ketan|K|', 'Haj-Ahmad|Rita|R|', 'Charalambopoulou|Georgia|G|', 'Steriotis|Theodore|T|', 'Giasafaki|Dimitra|D|', 'Cox|Paul|P|', 'Singh|Neenu|N|', 'Giassafaki|Lefki-Pavlina N|LN|', 'Mpenekou|Aggeliki|A|', 'Markopoulou|Catherine K|CK|', 'Vizirianakis|Ioannis S|IS|', 'Chang|Ming-Wei|MW|', 'Fatouros|Dimitrios G|DG|', 'Ahmad|Zeeshan|Z|']
D000818:Animals D000970:Antineoplastic Agents D018938:Caco-2 Cells D002626:Chemistry, Pharmaceutical D003460:Crystallization D004337:Drug Carriers D065546:Drug Liberation D006801:Humans D007408:Intestinal Absorption D008297:Male D016062:Porosity D051381:Rats D017208:Rats, Wistar D012822:Silicon Dioxide D012995:Solubility D012997:Solvents D013678:Technology, Pharmaceutical D014867:Water
Electrospraying Ex vivo Chalcones Electrohydrodynamic atomization Cytocompatibility Mesoporous silica Molecular modeling Poor solubility