5-Fluorouracil is a member of cytotoxic drugs with poor selectivity to cancer cells. Currently, systemic administration of this anti-cancer drug (oral or injection) exposes normal tissues to the drug-induced toxicity. Nowadays, attention has been greatly directed towards in situ gel-forming systems that can be injected into the affected tissues in its sol form with a minimally invasive technique. More specifically, chitosan hydrogel systems were in focus due to their antibacterial effect as well as their biodegradable, biocompatible, and mucoadhesive properties. In the present work, 5-fluorouracil was loaded on various thermosensitive chitosan hydrogel systems cross linked with different linking agents like β-glycerophosphate, pluronic F127, and hydroxyapatite. Also, methotrexate was added to 5-fluorouracil in order to gain its previously reported synergistic effects. Firstly, a compatibility study was performed using UV-spectrophotometric, infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) techniques to exclude the possibility of any physical or chemical interactions between the selected drugs and excipients. The prepared hydrogel systems were characterized for their physicochemical properties including organoleptic, pH, syringeability and injectability, viscosity, and gelation temperature (Tgel) by various analysis techniques. Moreover, the in vitro release behavior of 5-fluorouracil and methotrexate was determined with a modified analytical method. The results indicated that chitosan hydrogel system cross-linked with a combination of β- glycerophosphate, and 10 % pluronicF127 (F4) showed the most suitable physicochemical properties and release profile. Accordingly, this formula can be considered as a missionary system for localized sustained delivery of cytotoxic drugs.
The treatment of breast cancer requires long chemotherapy management, which is accompanied by severe side effects. Localized delivery of anticancer drugs helps to increase the drug concentration at the site of action and overcome such a problem. In the present study, chitosan hydrogel was prepared for local delivery of 5-Fluorouracil. The in vitro release behavior was investigated and the anticancer activity was evaluated against MCF-7 cells using MTT assay. The in vivo studies were investigated via intra-tumoral injection of a 5-FU loaded hydrogel into breast cancer of female rats. The results indicated that the modified hydrogel has excellent physicochemical properties with a sustained in vitro release profile matching a zero-order kinetic for one month. In addition, the hydrogel showed superior inhibition of cell viability compared with the untreated control group. Moreover, the in vivo studies resulted in antitumor activity with minor side effects. The tumor volume and level of tumor markers in blood were inhibited significantly by applying the hydrogel compared with the untreated control group. In conclusion, the designed injectable hydrogels are potential drug delivery systems for the treatment of breast cancer with a controlled drug release profile, which could be suitable for decreasing the side effects of chemotherapy agents.
30 June 2023 in International Journal of Biological Macromolecules
In this study, the carbon sphere (Cs) has been prepared and modified by titania nanotubes (TNTs) to be utilized as an adsorbent toward crystal violet (CV) dye as a model for cationic dyes from aqueous solution. The prepared TNTs@Cs composites has been characterized by various techniques such as XRD, SEM, and TEM analysis. The adsorption analysis displayed that the adsorption capacity of CV dye onto the modified Cs with TNTs is 92.5 mg g−1, which is much higher than that achieved by pristine Cs (12.5 mg g−1). Various factors that influence the overall adsorption processes, such as pH, contact time, initial CV dye concentration, adsorbent weight, and temperature, were studied. The TNTs@Cs76.7 composite showed the highest removal percentage of 99.00% at optimum conditions. The adsorption isotherm analysis showed that the experimental data of adsorption CV dye fitted better with the Langmuir isotherm model with R2 of 0.999, and the estimated maximum adsorption capacity was 84.7 mg g−1. On the other hand, the adsorption kinetic study showed that the adsorption of CV follows the pseudo-second order kinetic model with an equilibrium adsorption capacity (qe) of 10.66, 18.622, 47.61, and 48.31 mg g−1 for Cs, TNTs@Cs93, TNTs@Cs86.8, and TNTs@Cs76.7 composites, respectively. The thermodynamic analysis showed negative free energy (ΔG) values, this indicates that the adsorption of CV is a spontaneous and feasible process. Furthermore, the ΔH and ΔS are positive values that indicate an endothermic adsorption process. Furthermore, the prepared TNTs@Cs76.7 composite displayed remarkable adsorption stability and the removal efficiency of CV remains at 96.3% after five cycles.
Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host β-cyclodextrin polymers (8armPEG20k-CD and pβ-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies.