pH-Sensitive mesoporous zirconium diphosphonates for controllable colon-targeted delivery

Abstract

pH-Sensitive mesoporous zirconium diphosphonates have been successfully synthesized through the surfactant-assisted procedure using the organophosphonate derivative of piperazine, 1,4-bis(phosphomethyl)piperazine (BPMP), and ZrCl₄ as the metal precursor. The pH-sensitivity was derived from the reversible protonation–deprotonation of piperazine groups integrated in the mesoporous walls under different pH values, which endows mesoporous zirconium diphosphonates with reversible cationic–neutral surface properties. These pH-sensitive materials can effectively adsorb PDS (dinuclear cobalt phthalocyanine ammonium sulfonate, a photosensitizer of sulfonated phthalocyanine for photodynamic therapy of tumors) through strong electrostatic interaction. The PDS-loaded samples exhibit pH-dependent release behaviors for PDS in physiological buffer solutions as evidenced by the fact that almost no PDS release can be observed in simulated gastric fluid (pH 1.2) and a sustained release of PDS with a slower initial release rate was triggered with the electrostatic interaction disappearing due to the deprotonation of piperazine groups in the mesoporous walls under the weakly basic medium of simulated intestinal fluid (pH 7.5). The pH-sensitive mesoporous zirconium diphosphonates as smart carriers for pH-controllable release of anionic photosensitizer can be used to develop an oral colon-targeted drug delivery system in which the drug molecules will be trapped without release when passing through the stomach, and be released completely in a sustained-release method in the colon followed by a minimal drug release in the small intestine.