Polymer Induced Gelation of Aqueous Suspensions of Cellulose Nanocrystals.

We investigated the gelation of cellulose nanocrystals (CNCs) in polyelectrolyte and neutral polymer solutions. Cellulose nanocrystals (CNCs) with half-ester sulfate groups produced by acid hydrolysis of wood pulp were used in this study. The microstructure of CNCs/polymer suspensions was investigated in semidilute concentration regimes by selecting carboxymethyl cellulose (CMC700) as an anionic polymer and poly(ethylene oxide) (PEO600) as a neutral polymer solution. Together with quartz crystal microbalance with dissipation monitoring (QCM-D), rheology, scanning electron microscopy (SEM), and cryo-transmission electron microscopy (cryo-TEM), we characterized CNCs-polymer interactions, the suspension microstructure, and the macroscopic gel flow. Significant viscosity increases at low shear rates coupled with high shear-thinning behaviors were observed in CNC colloid-CMC700 polymer mixtures, but not those CNCs in PEO600 solutions. The apparent differences between CNCs-CMC700 and CNCs-PEO600 mixtures were due to their chain confirmations. On the basis of the evaluations from STEM, cryo-TEM, and polarized optical microscopy, we proposed that the excess CMC700 molecules in solutions result in the depletion of CNCs and the formation of anisotropic domains.

Exploring the gelation of aqueous cellulose nanocrystals (CNCs)-hydroxyethyl cellulose (HEC) mixtures.

We investigated the gelation and microstructure of cellulose nanocrystals (CNCs) in nonionic hydroxyethyl cellulose (HEC) solutions. Cellulose nanocrystals (CNCs) with a particle length of 90 nm and width of 8 nm currently produced by acid hydrolysis of wood pulp were used in this study. The microstructures of CNCs/polymer suspensions were investigated by performing linear small amplitude oscillatory shear (SAOS) and nonlinear large amplitude oscillatory shear (LAOS), in addition to constructing CNCs phase diagrams and measuring steady-state shear viscosities. Significant viscosity increases at low shear rates coupled with high shear thinning behaviors were observed in CNCs in HEC solutions above the overlapping concentration of HEC. The physical strength of CNCs/HEC solution gels increased with the increase in CNCs concentration and resembled the weakly crosslinked gels according to the scaling of linear dynamic mechanical experiments. According to LAOS analysis, CNCs/HEC mixtures showed type III behavior with intercycle stress softening, while the samples showed stress stiffening in single cycles.

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2.

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.

Spray-dried microparticles of encapsulated gefitinib for slow-release localized treatment of periodontal disease.

Periodontal disease (PD) can be prevented by local or systemic application of epidermal growth factor receptor inhibitors (EGFRIs) that stabilize αvß6 integrin levels in the periodontal tissue, leading to an increase in the expression of anti-inflammatory cytokines, such as transforming growth factor-ß1. Systemic EGFRIs have side effects and, therefore, local treatment of PD applied into the periodontal pockets would be preferrable. Thus, we have developed slow-release three-layered microparticles of gefitinib, a commercially available EGFRI. A combination of different polymers [cellulose acetate butyrate (CAB), Poly (D, L-lactide-co-glycolide) (PLGA) and ethyl cellulose (EC)] and sugars [D-mannose, D-mannitol and D-(+)-trehalose dihydrate] were used for the encapsulation. The optimal formulation was composed of CAB, EC, PLGA, mannose and gefitinib (0.59, 0.24, 0.09, 1, and 0.005 mg/ml, respectively; labeled CEP-gef), and created microparticles of 5.7 ± 2.3 µm in diameter, encapsulation efficiency of 99.98%, and a release rate of more than 300 h. A suspension of this microparticle formulation blocked EGFR phosphorylation and restored αvß6 integrin levels in oral epithelial cells, while the respective control microparticles showed no effect.

Engineered dry powders for the nose-to-brain delivery of transforming growth factor-beta.

Nose-to-brain delivery is increasing in popularity as an alternative to other invasive delivery routes. However, targeting the drugs and bypassing the central nervous system are challenging. We aim to develop dry powders composed of nanoparticles-in-microparticles for high efficiency of nose-to-brain delivery. The size of microparticles (between 250 and 350 µm), is desired for reaching the olfactory area, located below the nose-to-brain barrier. Moreover, nanoparticles with a diameter between 150 and 200 nm are desired for traveling through the nose-to-brain barrier. The materials of PLGA or lecithin were used in this study for nanoencapsulation. Both types of capsules showed no toxicology on nasal (RPMI 2650) cells and a similar permeability coefficient (Papp) of Flu-Na, which was about 3.69 ± 0.47 × 10-6 and 3.88 ± 0.43 × 10-6 cm/s for TGF-ß-Lecithin and PLGA, respectively. The main difference was related to the location of deposition; the TGF-ß-PLGA showed a higher drug deposition in the nasopharynx (49.89 ± 25.90 %), but the TGF-ß-Lecithin formulation mostly placed in the nostril (41.71 ± 13.35 %).

Sprayable cellulose nanofibrils stabilized phase change material Pickering emulsion for spray coating application.

Phase change materials (PCM) have been increasingly used over the past decades in applications requiring thermal energy storage or maintaining temperature uniformity, in particular in the textile industry. Organic PCM is desired in temperature control, but it suffers from thermal leaking and unstable form during phase transition. Here, cellulose nanofibrils (CNFs) were used as emulsifiers to stabilize paraffin Pickering emulsion by ultrasonication. Results indicated uniform PCM emulsion particles of 4.2 ± 2.1 µm could be obtained using 0.8 wt% CNF suspension sonicated at 100%A and 7 mins with 2:8 paraffin to CNF ratio. The CNF-stabilized paraffin emulsion showed excellent long-term stability with unchanged particle size when stored at 45 °C for 28 days. In addition, differential scanning calorimetry (DSC) results showed high thermal stability after 51 heating-cooling cycles with high latent heat of 117.6 J/g. The CNF-stabilized paraffin emulsion can be facilely spray-coated onto fabric to prepare thermal regulating textile.

Engineered nasal dry powder for the encapsulation of bioactive compounds.

In this review, we present the potential of nasal dry powders to deliver stable bioactive compounds and their manufacture using spray-drying (SD) techniques to achieve encapsulation. We also review currently approved and experimental excipients used for powder manufacturing for specific target drugs. Polymers, sugars, and amino acids are recommended for specific actions, such as mucoadhesive interactions, to increase residence time on the nasal mucosa; for example, high-molecular weight polymers, such as hydroxypropyl methylcellulose, or mannitol, which protect the bioactive compounds, increase their stability, and enhance drug absorption in the nasal mucosa; and leucine, which promotes particle formation and improves aerosol performance.

Antifouling, antibacterial and non-cytotoxic transparent cellulose membrane with grafted zwitterion and quaternary ammonium copolymers.

Copolymer brushes with different ratios of sulfobetaine methacrylate (SBMA) and [2-(Acryloyloxy)ethyl]trimethylammonium chloride (DAC) were grafted from transparent cellulose membrane (CM) via surface-initiated atom transfer radical polymerization (SI-ATRP) method for improving its antifouling and antibacterial performance. Surface concentrated copolymer grafting on the cellulose membranes can be obtained without significantly sacrificing the transparency and mechanical properties. The zwitterionic PSBMA chains of the copolymers can lead to an extremely hydrophilic surface with significantly reduced non-specific protein adsorption and bacterial attachment, therefore, leading to satisfying antifouling and antibacterial property. While the PDAC chains of the copolymers improved antibacterial performance against both Gram-positive and Gram-negative bacteria due to the presence of quaternary ammonium groups, the PDAC modified CM (CM-1) possessed best antibacterial performance, reaching to 95.1 % against S. aureus and 90.5 % against E. coli, respectively. More importantly, the biocompatibility of all grafted CM was retained, leading to over 100 % cell viability.

Acidic deep eutectic solvent assisted isolation of lignin containing nanocellulose from thermomechanical pulp.

Nanocellulose is a promising material but its isolation generally requires unrecyclable hazardous chemicals and high energy consumption and its overall yield is low due to the use of high purity cellulose as precursor. In order to overcome these shortcomings, in this study, thermomechanical pulp (TMP) was investigated as a precursor for isolating lignin containing nanocellulose (LNC) using an environmentally friendly acidic deep eutectic solvent (DES) pre-treatment. Flat "ribbon" like LNCs (around 7.1 nm wide, 3.7 nm thick) with uniformly distributed lignin nanoparticles of 20-50 nm in diameter were successfully obtained at 57 % yield under optimum pre-treatment conditions (90 °C, 6 h, 1:1 oxalic acid dihydrate to choline chloride ratio). The LNCs exhibit cellulose Iß structure, high lignin content (32.6 %), and high thermal stability (Tmax of 358 °C). In general, green acidic DES pre-treatment has shown high efficiency in converting high lignin content biomass into value-added LNC, which benefits both lignocellulose utilization and environmental protection.