Preparation and characterization of functionalized heparin-loaded poly-Ɛ-caprolactone fibrous mats to prevent infection with human papillomaviruses.

Abstract

In this study, heparin-loaded poly-ɛ-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was obtained via heparin crosslinking. This was achieved by running a carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction on preformed PCL fibers. In vitro HPV16 L1 protein binding capacity studies were performed. Infectivity assays were done using HPV16 pseudoviruses (PsVs) carrying a GFP plasmid to directly test the ability of the fibrous mats to prevent internalization of HPV PsVs. The crosslinked heparin material presented a dissociation constant (Kd) value comparable to those found in the literature for different heparin-protein L1 peptide interactions. Both materials significantly reduced internalization of HPV PsVs, with a reduction of 94% of PsVs internalization when matrix encapsulated heparin-loaded material was present. Differences in performance between the two proposed structures are discussed.