Hybrid nanofibers based on poly-caprolactone/gelatin/hydroxyapatite nanoparticles-loaded Doxycycline: Effective anti-tumoral and antibacterial activity.

Cancer is one of the leading causes of morbidity and mortality Worldwide, 19.3 million new cancer cases are expected to be identified in 2025. Among the therapeutic arsenal to cancer control one could find the Doxycycline and the nano hydroxyapatite. The Doxycycline (Dox) not only shown antibiotic effect but also exhibits a wide range of pleiotropic therapeutic properties as the control of the invasive and metastatic cancer cells characteristics. The purpose of the present study was to evaluate both cytotoxicity in vitro and antibacterial activity of electrospun Dox-loaded hybrid nanofibrous scaffolds composed by hydroxyapatite nanoparticles (nHA), poly-ε-caprolactone (PCL) and gelatin (Gel) polymers. Both nHA and Dox were dispersed into different PCL/Gel ratios (70:30, 60:40, 50:50wt%) solutions to form electrospun nanofibers. The nHA and Dox/nHA/PCL-Gel hybrid nanofibers were characterized by TEM microscopy. In vitro Dox release behavior from all of these Dox-loaded nHA/PCL-Gel nanofibers showed the same burst release profile due to the high solubility of Gel in the release medium. Antibacterial properties of nanofiber composites were evaluated using Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Porphyromonas gingivalis (P. gingivalis) bacteria. The co-delivery of nHA particles and Dox simultaneously exhibited inhibition of bacterial growth more efficiently than the delivery of either Dox or nHA at the same concentrations, indicating a synergistic effect. The results showed that cancer cell tested had different sensibility to co-delivery system. On the whole, A-431 cells were found exhibited the most pronounced synergistic effect compared to CACO-2 and 4T1 cancer cells. Based on the anticancer as well as the antimicrobial results in this study, the developed Dox/nHA/PCL-Gel composite nanofibers are suitable as a drug delivery system with potential applications in the biomedical fields.