Formation of Toroidal-Spiral Particles: Toward Parallel Pathways for Sustained Multi-Drug Release

The self-assembly of polymeric particles, whereby competitive kinetics of viscous sedimentation, diffusion and cross linking yield a controllable toroidal-spiral particle (TSP). The intricate internal spiral channels form because low interfacial tension between two miscible solutions is dominated by viscous forces. The width of the channels are controlled by Weber number during droplet impact on the surface, and Reynolds number and viscosity ratio during subsequent sedimentation. The biocompatible polymer, poly(ethylene glycol) diacrylate (PEGDA), was used to demonstrate the solidification of the toroidal spiral shapes at various configurational stages by UV-triggered cross linking. TSPs were also fabricated by the interaction of two vertically displaced drops sedimenting in a miscible solution. This system provided more flexibility and better control for encapsulation of cytotoxic and expensive compounds. TSPs provide a platform for encapsulation and release of multiple therapeutic compounds of different sizes and physicochemical properties. As a model system, the encapsulation and independently controlled release of an anti-VEGFR-2 antibody and irinotecan for the treatment of glioblastoma multiforme is demonstrated. Sufficient binding of anti-VEGFR-2 antibody released from the TS channels to HUVECs as confirmed by confocal microscopy and flow cytometry suggests active antibody encapsulation and release. Irinotecan released form the dense polymeric matrix of the TSP showed efficient U251 malignant glioma cell growth inhibition for approximately one week. Since the therapeutic compounds are released through different pathways, specifically diffusion through the polymer matrix versus TS channels, the release rates are controlled separately through design of the structure and material. The TSP provides substantial improvement in the design of biomaterials for drug delivery of multiple therapeutics of varying physicochemical properties by providing parallel routes for controlled drug release.