Preparação e caracterização de matrizes de liberação controlada de doxiciclina à base de nanofibras de policaprolactona e gelatina carreadas com nanopartículas de hidroxiapatita

Abstract

One of the most important stages of tissue engineering (TE) is the design and processing of a porous, biodegradable three-dimensional scaffolds. There is an increasing need for materials which having the potential capacity for the controlled delivery of drugs and at the same time provide structural support for cells. Thus improve a tissue-implant interface leading to the integration of the biomaterial. In thiscontext, electrospinning is recognized as an efficient technique for the fabrication of nanofibers that can be used to obtain scaffoldos that mimicking extracellular matrix and promote cell growth. On the other hand, hydroxyapatite (HA) is one of the most biocompatible ceramics due to its structural and chemical similarity with the mineralcomponents of human bones and teeth, and that way has been used to manufacture numerous implants. In the present study, poly ("-caprolactone) (PCL) / gelatin (GEL) nanofiber were produced with the use of electrospinning technique. Polymer were dissolved usingdiluted acetic and ethyl acetate mixture. Well dispersed nanoparticles of HA powders and Doxycicline (Dox) were then mixed with the PCL/GEL solution, and the final solution was electrospun. Hydroxyapatite was synthesized by co-precipitation method with and without adding Pluronic F127, used it as non- ionic surfactant. The HA was subjected to several heat-treatment process. The Dox is a broad spectrum antibioticused as a therapeutic agent in order to reduce the risk of infection associated with the biomaterial implants procedures in tissue engineering applications. Fibers and HA were characterized by various physicochemical techniques: Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible Spectroscopy (UV-Vis), thermal analysis (TG, DTG, DTA), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM). In the caseof HA, Nitrogen adsorption measurements (BET) and for the fibers contact-angle measurements was made. TEM micrographs revealed that the synthesized nanoparticles of HA (nHA) was homogeneous and rod-like particles, with a diameter of about 27.5 +- 6.6 nm, a lengthof 39.6 +- 16.8 nm. On the other hand, the nanoparticles obtained were thermally treated at various temperatures. The influence of temperature on structural, textural, and morphological properties of the materials was studied. In this comparative investigation, three types of PCL/GEL-based scaffolds were engineered: the PCL/GEL, PCL/GEL-HA and PCL/GEL-HA-Dox. Nanofibers were examined using a field emission scanning electron microscope (FESEM) for the fiber size and morphology. The incorporation of nHAs within the fibers didnt affect thesize of nanofibers. The average diameter of fibers PCL/GEL and PCL/GEL-HA were respectively 401+- 181 and 485 +- 144 nm. TEM imagens showed fibers composed of two polymer phases but the blend was compatible MTT assay results showed that doxycycline eluted from fibers was concentrationdependent cytotoxicity against Human epidermoid carcinoma cell A431 and L929 mouse fibroblasts after 24 and 48 hours of treatment. Likewise, the fibers showedinhibition zone on an agar plate of bacterial culture of against S. aureus and P. gingivalis.