Preparation of injectable hydrogel based on gelatin- gellan gum containing quantum dots for effective drug delivery of 5-fluorouracil

Abstract

The second deadliest type of cancer in women is breast cancer. There are various methods to treat breast cancer, such as surgery, chemotherapy, radiation therapy, immunotherapy, gene therapy, and hormone therapy. In most cases, surgery is used to remove cancerous tissue and chemotherapy. These treatments alone or in combination are useful to prevent relapse. Various systems such as hydrogels, micelles, nanoparticles, niosomes and liposomes were investigated for local drug delivery. In recent years, hydrogels have attracted a lot of attention as one of the most promising drug delivery systems due to their unique potential (hydrophilicity and very high water content) through combination with a nanoparticle. Such polymeric hydrogel nanoparticle systems have been prepared and characterized based on natural and synthetic polymers in recent years. Natural polymers include gelan gum, alginate, gelatin, hyaluronic acid etc., and artificial polymers include polyvinyl alcohol, polyethylene glycol, polyhydroxyl methacrylate and polyvinyl pyrrolidans. Graphene quantum dots (GQDs) have important features such as distinct shapes, isotropic with very fine dimensions and easily modifiable surface functionalities, physicochemical properties and fluorescence. 5-fluorouracil (5-FU) has become a key anticancer drug that has been used to treat various types of malignancies for its broad antitumor activity, as well as its synergism with other anticancer drugs.Target: In this research, hydrogels based on oxidized gelatin-gellan gum will be prepared and their capability in the controlled release of anti-cancer drug 5-fluorouracil (5-FU) will be investigated to destroy breast cancer cells. In addition, GQDs will be used as imaging agents, which have fluorescence properties and can emit bright and stable fluorescence when excited by a UV source. By loading GQDs into hydrogel drug delivery systems, drug movement and distribution can be tracked in time, enabling visualization of drug delivery pathways, targeted aggregation and monitoring of drug release.Research Methodology: This research aims to develop injectable hydrogels composed of natural polymers, gelatin, and oxidized gellan gum, loaded with graphene quantum dots (GQDs) and an anti-cancer drug. A comprehensive characterization of the synthesized hydrogels will be conducted using Fourier Transform Infrared (FT-IR) spectroscopy to confirm functional group formation, Scanning Electron Microscopy (SEM) to analyze surface morphology, Dynamic Light Scattering (DLS) to determine particle size and zeta potential, and Rheology to assess mechanical properties. Additionally, the fluorescence properties of GQDs and the cytotoxicity of the hydrogels will be evaluated using fluorescence spectroscopy and the MTT assay, respectively.Results: FT-IR spectroscopy confirmed the successful oxidation of gellan gum, the subsequent Schiff base reaction with gelatin, and the formation of a hydrogel network. Graphene quantum dots (GQDs) exhibited a particle size of 48.73 nm and a zeta potential of -36.6 mV. Rheological analysis revealed that the hydrogel displayed enhanced elastic behavior, as indicated by a higher storage modulus (G'). Furthermore, the hydrogel demonstrated favorable swelling properties, biocompatibility, and degradability, making it a promising candidate for drug delivery applications. The GQDs exhibited strong fluorescence emission at 465 nm upon excitation at 365 nm. Cytotoxicity assays (MTT) confirmed the excellent biocompatibility of the hydrogels with MCF-7 cells, with cell viability exceeding 80%.