Release of amoxicillin and doxycycline from PLA nanofibers optimized using factorial experimental design

Due to their excellent properties, active material-loaded nanofibers have gained tremendous attention because of their important role in biomedicine, such as wound dressing, tissue engineering, and drug delivery. This study was conducted to obtain polylactic acid (PLA) nanofibers by electrospinning after finding the optimal parameters by factorial experimental design. Moreover, the new hydroxyapatite (HAP)@PLA-based nanofiber containing two antibiotics (amoxicillin, Amox, and doxycycline, Dox) was designed to ensure a prolonged effect of the adsorbed antibiotic (Dox), while the encapsulated antibiotic (Amox) is released subsequent Dox to eliminate the bacteria resistant to Dox. In this regard, the release kinetics of the two different antibiotics (Amox and Dox) co-loaded on (HAP)@PLA-based nanofibers were studied in artificial saliva (AS), physiological saline solution (PSS) and simulated body fluid (SBF) up to 21 days. The concentration and flow rate displayed the most significant effect, while distance and voltage presented the most negligible effect. In the first stage, the Dox released rapidly with a burst effect, suggesting that the release of drug adsorbed on the nanofiber surface can easily detach and release in the medium, while the second phase involved the sustained Amox release from the nanofiber. This effect was more visible when using AS as release media. Finally, zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas models were used to explain the Amox and Dox release behavior of HAP/Amox/Dox@PLA nanofibers. The zero-order, Higuchi, and Korsmeyer-Peppas models showed acceptable regression values for Amox and Dox release from HAP/PLA nanofibers at 15 days. Moreover, the combination of Amox and Dox could exert a synergistic antibacterial effect, thus providing a new strategy to increase the therapeutic efficacy against periodontopathogenic bacteria. The promising results suggest using these new nanofibers as a compelling candidate for the treatment of periodontitis.