A review of recent advances of cellulose-based intelligent-responsive hydrogels as vehicles for controllable drug delivery system.

To realize the maximum therapeutic activity of medicine and protect the body from the adverse effects of active ingredients, drug delivery systems (DDS) featured with targeted transportation sites and controllable release have captured extensive attention over the past decades. Hydrogels with unique three-dimensional (3D) porous structures present tunable capacity, controllable degradation, various stimuli sensitivity, therapeutic agents encapsulation, and loaded drugs protection properties, which endow hydrogels with bred-in-the-bone advantages as vehicles for drug delivery. In recent years, with the impressive consciousness of the "back-to-nature" concept, biomass materials are becoming the 'rising star' as the hydrogels building blocks for controlled drug release carriers due to their biodegradability, biocompatibility, and non-toxicity properties. In particular, cellulose and its derivatives are promising candidates for fabricating hydrogels as their rich sources and high availability, and various smart cellulose-based hydrogels as targeted carriers under exogenous such as light, electric field, and magnetic field or endogenous such as pH, temperature, ionic strength, and redox gradients. In this review, we summarized the main synthetic strategies of smart cellulose-based hydrogels including physical and chemical cross-linking, and illustrated the detailed intelligent-responsive mechanism of hydrogels in DDS under external stimulus. Additionally, the ongoing development and challenges of cellulose-based hydrogels in the biomedical field are also presented.

Enhanced curcumin loaded nanocellulose: a possible inhalable nanotherapeutic to treat COVID-19.

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.

Electro-Stimulated Release of Poorly Water-Soluble Drug from Poly(Lactic Acid)/Carboxymethyl Cellulose/ZnO Nanocomposite Film.

PURPOSE: Among various types of external stimuli-responsive DDS, electric-responsive DDS are more promising carriers as they exploit less complex, easily miniaturized electric signal generators and the possibility of fine-tuning the electric signals. This study investigates the use of intrinsically biocompatible biopolymers in electro-simulative drug delivery to enhance the release of poorly-soluble/non-ionic drug. METHODS: CMC/PLA/ZnO/CUR nanocomposite films were prepared by the dispersion of CMC and ZnO NPs in solubilized PLA/curcumin medium, followed by solvent casting step. Curcumin is poorly water-soluble and used as the model drug in this study. The films with different contents of CMC, PLA and ZnO NPs were characterized using FTIR, impedance spectroscopy, tensile testing and FESEM imaging. The in vitro drug release of the films was carried out in deionized water under DC electric field of 4.5 V. RESULTS: The ionic conductivity of the films increased with increasing the CMC concentration of the film. The addition of a small amount of ZnO NPs (2%) successfully restored the tensile properties of the film. In response to the application of the electric field, the composite films released drug with a near-linear profile. There was no noticeable amount of passive diffusion of the drug from the film with the absence of the electric field. CONCLUSION: The outcome of this study enabled the design of an electric-responsive nanocomposite platform for the delivery of poorly water-soluble/non-ionic drugs. Graphical abstract.

Fabrication of Polycaprolactone/Polyurethane Loading Conjugated Linoleic Acid and Its Antiplatelet Adhesion.

Polycaprolactone/polyurethane (PCL/PU) fibrous scaffold was loaded with conjugated linoleic acid (CLA) by electrospinning method to improve the hemocompatibility of the polymeric surface. Fourier Transform Infrared Spectroscopy (FT-IR) analysis and Scanning Electron Microscopy (SEM) observation were employed to characterize the chemical structure and the changing morphology of electrospun PCL/PU and PCL/PU loaded with CLA (PCL/PU-CLA) scaffolds. Platelet adhesion and whole blood clot formation tests were used to evaluate the effect of CLA on antithrombotic property of PCL/PU-CLA scaffold. Endothelial cells (EC) were also seeded on the scaffold to examine the difference in the morphology of EC layer and platelet attachment with and without the presence of CLA. SEM results showed that CLA supported the spreading and proliferation of EC and PCL/PU-CLA surface induced lower platelet adhesion as well as attachment of other blood cells compared to the PCL/PU one. These results suggest that electrospinning method can successfully combine the antiplatelet effects of CLA to improve hemocompatibility of PCL/PU scaffolds for applications in artificial blood vessels.