Superhydrophobic materials for tunable drug release: using displacement of air to control delivery rates

Abstract

We have prepared 3D superhydrophobic materials from biocompatible building blocks, where air acts as a barrier component in a porous electrospun mesh to control the rate at which drug is released. Specifically, we fabricated poly(ε-caprolactone) electrospun meshes containing poly(glycerol monostearate-co-ε-caprolactone) as a hydrophobic polymer dopant, which results in meshes with a high apparent contact angle. We demonstrate that the apparent contact angle of these meshes dictates the rate at which water penetrates into the porous network and displaces entrapped air. The addition of a model bioactive agent (SN-38) showed a release rate with a striking dependence on the apparent contact angle that can be explained by this displacement of air within the electrospun meshes. We further show that porous electrospun meshes with higher surface area can be prepared that release more slowly than control nonporous constructs. Finally, the entrapped air layer within superhydrophobic meshes is shown to be robust in the presence of serum, as drug-loaded meshes were efficacious against cancer cells in vitro for >60 days, thus demonstrating their applicability for long-term drug delivery.

Figure 1

(A) PCL was used as the base polymer for fabrication of electrospun meshes and melted electrospun meshes. (B) PGC-C18 was used as the hydrophobic dopant in PCL electrospun meshes to decrease the wettability of the meshes. (C) Electrospun PCL mesh with an average fiber size of 7.7±1.2 μm. (D) 10% doped PGC-C18 electrospun PCL mesh with an average fiber size of 7.2±1.4 μm. (E) A melted PCL mesh. (F) A melted 10% doped PGC-C18 electrospun PCL mesh.

Figure 2

Contact angle measurements of electrospun meshes and chemically equivalent smooth surfaces as a function of PGC-C18 doping. The black dashed line indicates an approximate boundary for the Wenzel-Cassie state transition.

Figure 3

Release profiles comparing SN-38 release between (A) native, melted and degassed PCL electrospun meshes, and (B) native, melted and degassed 10% PGC-C18 doped PCL electrospun meshes as well as higher PGC-C18 doping concentration of 30 and 50 wt%.

Figure 4

CT scans of native electrospun and degassed electrospun meshes with 0 or 10% PGC-C18 doping after incubation with the contrast agent Hexabrix for 2 hours. Degassed meshes exhibit full water penetration, while native and melted meshes (not shown) show only a low surface concentration of water. Tic marks define the top and bottom boundaries of the meshes.

Figure 5

Proposed mechanism of a drug-eluting 3D superhydrophobic material in a metastable Cassie state. Over time, water slowly displaces air content from the material with the transition from the metastable Cassie state to the stable Wenzel state. If treated as iterative surfaces, water will slowly penetrate each individual surface over time enabling prolonged drug release.

Figure 6

Cell cytotoxicity profiles when incubated with PCL meshes and PCL meshes with 10% PGC-C18 doping containing (A) 1 wt% or (B) 0.1 wt% SN-38. Both chemistries effectively treated LLC cells for 90 days at 1 wt% SN-38. By decreasing SN-38 concentration by 10-fold a significant difference in performance was observed, where PCL meshes were cytotoxic to LLC cells for 25 days, and the addition of 10% PGC-C18 to PCL meshes showed cytotoxicity for 65 days. Unloaded meshes were not cytotoxic to cells.