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

Ebtesam W Elsayed; Ahmed A El-Ashmawy; Gehan T El-Bassyouni; Sahar M Mousa; M El-Manawaty; Laila H Emara

doi:10.1016/j.ijbiomac.2023.124147

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

Int J Biol Macromol. 2023 May 15:237:124147. doi: 10.1016/j.ijbiomac.2023.124147. Epub 2023 Mar 23.

Authors

Ebtesam W Elsayed¹, Ahmed A El-Ashmawy², Gehan T El-Bassyouni³, Sahar M Mousa⁴, M El-Manawaty⁵, Laila H Emara²

Affiliations

¹ Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir St.), Dokki, Giza, Egypt. Electronic address: ebtesam.wahman@yahoo.com.
² Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir St.), Dokki, Giza, Egypt.
³ Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir St.), Dokki, Giza, Egypt.
⁴ Inorganic Chemistry Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir St.), Dokki, Giza, Egypt.
⁵ Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir St.), Dokki, Giza, Egypt.

PMID: 36965558
DOI: 10.1016/j.ijbiomac.2023.124147

Abstract

Alginate and gelatin are natural macromolecules used to formulate biocompatible drug delivery systems. Hydroxyapatite (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 scaffolds using different crosslinking solutions. 5-FU incorporation efficiency, in-vitro drug release, antitumor bioassays, 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.

Keywords: 5-fluorouracil; Crosslinked alginate-gelatin; Hydrogel scaffolds; Hydroxyapatite; Zn-doped hydroxyapatite.

MeSH terms

Alginates / chemistry
Durapatite* / chemistry
Fluorouracil
Gelatin* / chemistry
Hydrogels / chemistry
Tissue Scaffolds / chemistry
Zinc / chemistry

Substances

Durapatite
Gelatin
Zinc
Alginates
Hydrogels
Fluorouracil