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Preparation and characterization of functionalized heparin-loaded poly-ϵ-caprolactone fibrous mats to prevent human papilloma viral infections
Human Papillomavirus (HPV) is the most common sexually transmitted virus world-wide. Persistent infection with high-risk HPV types can induce cell abnormalities that could lead to the development of pre-cancerous lesions, or cancer of the cervix. Cervical cancer is the second most common cancer and the leading cause of cancer deaths in women in developing countries. Current approaches to reduce the incidence of cervical cancer involve cervical cancer screenings, and HPV prophylactic vaccines. However, neither HPV vaccines are effective in women who are already infected, nor they protect against all HPV types. This dissertation is aimed at developing a specific virus-binding material to prevent HPV infection. Two different approaches to produce heparin-loaded poly-ϵ-caprolactone (PCL) fibrous materials were applied in this study: one involved a simple matrix encapsulation of heparin (PCL-Hep), while the other one was based on the use of chemical cross-linking of heparin to the PCL backbone (PCL-Hep-CL, CL (crosslinked)). Both materials showed good biocompatibility, and the amount of immobilized heparin in the crosslinked mats was four times higher than that of the material based on matrix encapsulation. The incorporation of heparin improved the hydrophilicity of the materials, and also decreased polymer crystallinity. The PCL-Hep mats showed a sustained heparin release profile, while the heparin in PCL-Hep-CL was shown to be long-term stable. A high binding affinity for HPV16 L1 capsids (Kd=35 μM) was found in the crosslinked material. Infectivity assays with HPV16 pseudoviruses, carrying a green fluorescent protein (GFP) gene, demonstrated a 94% and 70% reduction in infection after incubation with the PCL-Hep and PCL-Hep-CL materials, respectively. The studies presented and discussed in this dissertation suggest that a heparin-loaded PCL material would be a promising candidate to prevent HPV infection. Such a material can potentially reduce the incidence of cervical cancer in millions of women that are already infected with HPV. These studies also suggest the possibility that this approach can be effective against other heparin-binding viruses.
Gonzalez, Daniela del Carmen, "Preparation and characterization of functionalized heparin-loaded poly-ϵ-caprolactone fibrous mats to prevent human papilloma viral infections" (2016). ETD collection for University of Nebraska - Lincoln. AAI10102688.