Abstract
In this study, 5-fluorouracil- (5-FU-) loaded hydroxyapatite-gelatin (HAp-GEL) polymer composites were produced in the presence of a simulated body fluid (SBF) to investigate the effects of temperature and cross-linking agents on drug release. The composites were produced by wet precipitation at pH 7.4 and temperature 37°C using glutaraldehyde (GA) as the cross-linker. The effects of different amounts of glutaraldehyde on drug release profiles were studied. Encapsulation (drug loading) was performed with 5-FU using a spray drier, and the drug release of 5-FU from the HAp-GEL composites was determined at temperatures of 32°C, 37°C, and 42°C. Different mathematical models were used to obtain the release mechanism of the drug. The morphologies and structures of the composites were analyzed by X-ray diffraction, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results demonstrated that for the HAp-GEL composites, the initial burst decreased with increasing GA content at all three studied temperatures. Further, three kinetic models were investigated, and it was determined that all the composites best fit the Higuchi model. It was concluded that the drug-loaded HAp-GEL composites have the potential to be used in drug delivery applications.
Highlights
Hydroxyapatite (HAp,Ca10(PO4)6(OH)2) is a biomaterial found in bone and teeth, which has an apatite-like structure [1, 2]
The obtained composites were characterized by XRD, TGA, FTIR, and SEM
Experimental stages consisted of the preparation of simulated body fluid (SBF) and phosphate buffer saline (PBS), the production of HAp-polymer composites in SBF with GA (two different ratios as 2% (v/v) and 5% (v/v)) as a cross-linking agent, the encapsulation of 5-FU in HAp-polymer using a spray dryer, and in vitro drug release in a PBS medium at different temperatures
Summary
Hydroxyapatite (HAp,Ca10(PO4)6(OH)2) is a biomaterial found in bone and teeth, which has an apatite-like structure [1, 2]. Because of its excellent chemical stability, biocompatibility, bioactivity, nontoxicity, and osteoconductivity, HAp has been used for the production of synthetic bone materials and bone and teeth implants and in drug delivery applications [2,3,4,5,6,7,8]. The highly brittle and stiff structure of HAp limits its usage in clinical applications [16, 17] These mechanical disadvantages can be overcome by adding a polymer. Biopolymers have excellent biocompatibility, more biodegradability, and adequate osteoconductivity [17, 24] Among these polymers, gelatin (GEL) is widely used in drug release systems alone or in composite form [25]. The porosity of HAp-GEL provides a high ratio of surface area to void
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