Encapsulation and release mechanisms in coordination polymer nanoparticles

The interplay of guest encapsulation and release mechanisms in nanoscale metal-organic vehicles and its effect on the drug-delivery kinetics of these materials were investigated through a new multidisciplinary approach. Two rationally-designed molecular guests were synthesized, which consist of a red-fluorescent benzophenoxazine dye covalently tethered to a coordinating catechol group and a protected, non-coordinating catechol moiety. This allowed loading of the guests into compositionally and structurally equivalent coordination polymer particles through distinct encapsulation mechanisms: coordination and mechanical entrapment. The two types of particles delivered their fluorescent cargo with remarkably different kinetic profiles, which could be satisfactorily modeled considering degradation- and diffusion-controlled release processes. This demonstrates that careful selection of the method of guest incorporation into coordination polymer nanoparticles allows selective tuning of the rate of drug delivery from these materials and, therefore, of the time window of action of the encapsulated therapeutic agents. Drug-release mechanisms uncovered! Coordination polymer nanoparticles loaded with coordinated and mechanically entrapped fluorescent guests were prepared as benchmark systems to investigate diffusion- and degradation-controlled drug delivery from these materials (see figure)

Encapsulation and release mechanisms in coordination polymer nanoparticles

The interplay of guest encapsulation and release mechanisms in nanoscale metal-organic vehicles and its effect on the drug-delivery kinetics of these materials were investigated through a new multidisciplinary approach. Two rationally-designed molecular guests were synthesized, which consist of a red-fluorescent benzophenoxazine dye covalently tethered to a coordinating catechol group and a protected, non-coordinating catechol moiety. This allowed loading of the guests into compositionally and structurally equivalent coordination polymer particles through distinct encapsulation mechanisms: coordination and mechanical entrapment. The two types of particles delivered their fluorescent cargo with remarkably different kinetic profiles, which could be satisfactorily modeled considering degradation- and diffusion-controlled release processes. This demonstrates that careful selection of the method of guest incorporation into coordination polymer nanoparticles allows selective tuning of the rate of drug delivery from these materials and, therefore, of the time window of action of the encapsulated therapeutic agents.We acknowledge the financial support of the “Ministerio de Economía y Competividad” (MINECO) through projects MAT2012–38318-C03–02, MAT2012–38319-C02–01, CTQ2012–30853 and CTQ2010–15380. L.A.-F. thanks the “Universitat Autónoma de Barcelona” for a pre-doctoral grant. F.N. thanks the “Ministerio de Economía y Competitividad” for a JdC (JCI-2011–09239) post-doctoral grant.Peer Reviewe