Formulation and evaluation of alginate-gelatin hydrogel scaffolds loaded with zinc-doped hydroxyapatite and 5-fluorouracil

Alginate and gelatin are natural macromolecules used to formulate biocompatible drug delivery systems. Hy-droxyapatite (HA) is an osteophilic ceramic used to prepare bone scaffolds. The current study aimed at preparing and characterizing HA, zinc-doped HA, and 5-fluorouracil(5-FU)-loaded alginate-gelatin-based hydrogel scaf-folds using different crosslinking solutions. 5-FU incorporation efficiency, in-vitro drug release, antitumor bio-assays, FTIR, X-ray-diffraction (XRD), High-Resolution Transmission, and Scanning-Electron Microscope (HR-TEM and SEM) studies were conducted. XRD showed the incorporation of Zn2+ into HA structure with a deformity in HA crystal lattice and inhibited crystal growth. FTIR-spectra represented the characteristic bands corresponding to HA structure. HR-TEM showed a decreased HA crystal size and rod-like crystallites that increased with increasing zinc content. Zn2+ content and 5-FU-loading caused significant effects on the scaffolds' thickness (p-value = 0.021 and 0.035, respectively). Burst 5-FU release within 10-15 min followed by 100 % release within 4 h was observed. Zinc content showed a significant positive effect on the cytotoxicity% of the blank and drug-loaded scaffolds. XRD and FTIR studies revealed that 5-FU was completely incorporated into the hydrogel with no chemical interaction. SEM-imaging showed interconnected pores and needle-shaped drug particles. The prepared formulations showed promising physico-chemical properties for targeted delivery of 5-FU in the form of biocompatible bone scaffolds.