A unique biodegradable, superporous, swellable and pH sensitive nanocellulose reinforced chitosan hydrogel with dynamic mechanical properties was prepared for oral administration of curcumin. Curcumin, a less water-soluble drug was used due to the fact that the fast swellable, superporous hydrogel could release a water-insoluble drug to a great extent. CO 2 gas foaming was used to fabricate hydrogel as it eradicates using organic solvents. Field emission scanning electron microscope images revealed that the pore size significantly increased with the formation of widely interconnected porous structure in gas foamed hydrogels. The maximum compression of pure chitosan hydrogel was 25.9 ± 1 kPa and it increased to 38.4 ± 1 kPa with the introduction of 0.5% cellulose nanocrystals. In vitro degradation of hydrogels was found dependent on the swelling ratio and the amount of CNC of the hydrogel. All the hydrogels showed maximum swelling ratios greater than 300%. The 0.5% CNC-chitosan hydrogel showed the highest swelling ratio of 438% ± 11%. FTIR spectrum indicated that there is no interaction between drug and ingredients present in hydrogels. The drug release occurred in non-Fickian (anomalous) manner in simulated gastric medium. The drug release profiles of hydrogels are consistent with the data obtained from the swelling studies. After gas foaming of the hydrogel, the drug loading efficiency increased from 41% ± 2.4% to 50% ± 2.0% and release increased from 0.74 to 1.06 mg/L. The drug release data showed good fitting to Ritger-Peppas model. Moreover, the results revealed that the drug maintained its chemical activity after in vitro release. According to the results of this study, CNC reinforced chitosan hydrogel can be suggested to improve the bioavailability of curcumin for the absorption from stomach and upper intestinal tract.

A poorly water-soluble anticancer drug, curcumin was loaded in to cellulose nanocrystals by dissolving it in a commonly used nonionic surfactant medium. Results showed that the drug loading capacity of nanocellulose increased with increasing the surfactant concentration of the medium.The drug loading capacity of nanocellulose in surfactant medium was significantly higher (7.73mg/g) when compared to the drug loading capacity (3.35mg/g) in methanolic medium. The nanocellulose drug loaded in surfactant medium (TW/CNC) showed higher drug release compared to the nanocellulose drug loaded in methanolic medium (METH/CNC). It was 8.99 mg/L for TW/CNC and 2.65 mg/L for METH/CNC in simulated gastric fluid. Due to the increased stability of curcumin in acidic medium, all the nanoparticles showed higher drug release in simulated gastric fluid compared to phosphate buffered saline solution. The maximum dissolution of curcumin was 2.13 mg/mL in distilled water containing 4% (w/v) of surfactant.UV-visible spectra revealed that the curcumin retained its chemical activity after in vitro release.From these findings, it is believed that the incorporation of curcumin into nanocellulose in surfactant medium provides a promising approach for delivery of curcumin to stomach and upper intestinal tract.

Graphical abstract Nanocellulose/polyvinyl alcohol/curcumin (CNC/PVA/curcumin) nanoparticles with enhanced drug loading properties were developed by the dispersion of nanocellulose in curcumin/polyvinyl alcohol aqueous medium. Due to the physical and chemical nature of sulphuric acid hydrolyzed nanocellulose and the antiviral properties of curcumin, the possibility of using these nanoparticles as an inhalable nanotherapeutic for the treatment of coronavirus disease 2019 (COVID-19) is discussed. The adsorption of curcumin and PVA into nanocellulose, and the presence of anionic sulphate groups, which is important for the interaction with viral glycoproteins were confirmed by Fourier transform infrared (FTIR) spectroscopy. FESEM images showed that the diameter of nanocellulose ranged from 50 to 100 nm, which is closer to the diameter (60–140 nm) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The solubility of poorly water-soluble curcumin was increased from 40.58 ± 1.42 to 313.61 ± 1.05 mg/L with increasing the PVA concentration from 0.05 to 0.8% (w/v) in aqueous medium. This is a significant increase in the solubility compared to curcumin’s solubility in carboxymethyl cellulose medium in our previous study. The drug loading capacity increased by 22-fold with the addition of 0.8% PVA to the nanocellulose dispersed curcumin solution. The highest drug release increased from 1.25 ± 0.15 mg/L to 17.11 ± 0.22 mg/L with increasing the PVA concentration from 0 to 0.8% in the drug-loaded medium. Future studies of this material will be based on the antiviral efficacy against SARS-CoV-2 and cell cytotoxicity studies. Due to the particulate nature, morphology and size of SARS-CoV-2, nanoparticle-based strategies offer a strong approach to tackling this virus. Hence, we believe that the enhanced loading of curcumin in nanocellulose will provide a promising nano-based solution for the treatment of COVID-19.

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