3D printing of responsive chiral photonic nanostructures.

Finely controlled flow forces in extrusion-based additive manufacturing can be exploited to program the self-assembly of malleable nanostructures in soft materials by integrating bottom-up design into a top-down processing approach. Here, we leverage the processing parameters offered by direct ink-writing (DIW) to reconfigure the photonic chiral nematic liquid crystalline phase in hydroxypropyl cellulose (HPC) solutions prior to deposition on the writing substrate to direct structural evolution from a particular initial condition. Moreover, we incorporate polyethylene glycol (PEG) into iridescent HPC inks to form a physically cross-linked network capable of inducing kinetic arrest of the cholesteric/chiral pitch at length scales that selectively reflect light throughout the visible spectrum. Based on thorough rheological measurements, we have found that printing the chiral inks at a shear rate where HPC molecules adopt pseudonematic state results in uniform chiral recovery following flow cessation and enhanced optical properties in the solid state. Printing chiral inks at high shear rates, on the other hand, shifts the monochromatic appearance of the extruded filaments to a highly angle-dependent state, suggesting a preferred orientation of the chiral domains. The optical response of these filaments when exposed to mechanical deformation can be used in the development of optical sensors.

Cholesteric cellulose liquid crystal ink for three-dimensional structural coloration.

SignificanceWe propose a printable structural color ink composed of cholesteric cellulose liquid crystals together with gelatin and a thermal-responsive hydrogel. The ink is endowed with vivid structural colors and printability due to its constituents. Based on this, we print a series of graphics and three-dimensional (3D) objects with vivid color appearances. Moreover, the printed objects possess dual thermal responsiveness, which results in visible color change around body temperature. These performances, together with the biocompatibility of the constituents, indicate that the present ink represents a leap forward to the next-generation 3D printing and would unlock a wide range of real-life applications.

Hierarchical Organization of Structurally Colored Cholesteric Phases of Cellulose via 3D Printing.

Structural color-a widespread phenomenon observed throughout nature is caused by light interference from ordered phases of matter. While state-of-the-art nanofabrication techniques can produce structural organization in small areas, cost-effective and scalable techniques are still lacking to generate tunable color at sub-micron length scales. In this work, structurally colored hydroxypropyl cellulose filaments are produced with a suppressed angular color response by 3D printing. The systematic study of the morphology of the filaments reveals the key stages in the induction of a two-degree hierarchical order through 3D printing. The first degree of order originated from the changing of the cholesteric pitch at a few hundred nm scale via chemical modification and tuning of the solid content of the lyotropic phase. Upon 3D printing, the secondary hierarchical order of periodic wrinkling is introduced through the Helfrich-Hurault deformation of the shear-aligned cholesteric phases. In single-layered filaments, four morphological zones with varying orders of wrinkles are identified. Detailed morphological characterization is carried out using SEM to shed light on the mechanism of the wrinkling behavior. Through this work, the possibility of modifying the wrinkling behavior is demonstrated and thus the angle dependence of the color response by changing the printing conditions.

In Situ Gelling Hydroxypropyl Cellulose Formulation Comprising Cannabidiol-Loaded Block Copolymer Micelles for Sustained Drug Delivery.

Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.

Dominant Factors Affecting Rheological Properties of Cellulose Derivatives Forming Thermotropic Cholesteric Liquid Crystals with Visible Reflection.

Hydroxypropyl cellulose (HPC) derivatives with alkanoyl side chains are known to form thermotropic cholesteric liquid crystals (CLCs) with visible reflection. Although the widely investigated CLCs are requisite for tedious syntheses of chiral and mesogenic compounds from precious petroleum resources, the HPC derivatives easily prepared from biomass resources would contribute to the realization of environment-friendly CLC devices. In this study, we report the linear rheological behavior of thermotropic CLCs of HPC derivatives possessing alkanoyl side chains of different lengths. In addition, the HPC derivatives have been synthesized by the complete esterification of hydroxy groups in HPC. The master curves of these HPC derivatives were almost identical at reference temperatures, with their light reflection at 405 nm. The relaxation peaks appeared at an angular frequency of ~102 rad/s, suggesting the motion of the CLC helical axis. Moreover, the dominant factors affecting the rheological properties of HPC derivatives were strongly dependent on the CLC helical structures. Further, this study provides one of the most promising fabrication strategies for the highly oriented CLC helix by shearing force, which is indispensable to the development of advanced photonic devices with eco-friendliness.

Hydroxypropyl Cellulose for Drug Precipitation Inhibition: From the Potential of Molecular Interactions to Performance Considering Microrheology.

There has been recent interest in using hydroxypropyl cellulose (HPC) for supersaturating drug formulations. This study investigated the potential for molecular HPC interactions with the model drug celecoxib by integrating novel approaches in the field of drug supersaturation analysis. Following an initial polymer characterization study, quantum-chemical calculations and molecular dynamics simulations were complemented with results of inverse gas chromatography and broadband diffusing wave spectroscopy. HPC performance was studied regarding drug solubilization and kinetics of desupersaturation using different grades (i.e., HPC-UL, SSL, SL, and L). The results suggested that the potential contribution of dispersive interactions and hydrogen bonding depended strongly on the absence or presence of the aqueous phase. It was proposed that aggregation of HPC polymer chains provided a complex heterogeneity of molecular environments with more or less excluded water for drug interaction. In precipitation experiments at a low aqueous polymer concentration (i.e., 0.01%, w/w), grades L and SL appeared to sustain drug supersaturation better than SSL and UL. However, UL was particularly effective in drug solubilization at pH 6.8. Thus, a better understanding of drug-polymer interactions is important for formulation development, and polymer blends may be used to harness the combined advantages of individual polymer grades.

Colorimetric Sensor Based on Hydroxypropyl Cellulose for Wide Temperature Sensing Range.

Recently, temperature monitoring with practical colorimetric sensors has been highlighted because they can directly visualize the temperature of surfaces without any power sources or electrical transducing systems. Accordingly, several colorimetric sensors that convert the temperature change into visible color alteration through various physical and chemical mechanisms have been proposed. However, the colorimetric temperature sensors that can be used at subzero temperatures and detect a wide range of temperatures have not been sufficiently explored. Here, we present a colorimetric sensory system that can detect and visualize a wide range of temperatures, even at a temperature below 0 °C. This system was developed with easily affordable materials via a simple fabrication method. The sensory system is mainly fabricated using hydroxypropyl cellulose (HPC) and ethylene glycol as the coolant. In this system, HPC can self-assemble into a temperature-responsive cholesteric liquid crystalline mesophase, and ethylene glycol can prevent the mesophase from freezing at low temperatures. The colorimetric sensory system can quantitatively visualize the temperature and show repeatability in the temperature change from -20 to 25 °C. This simple and reliable sensory system has great potential as a temperature-monitoring system for structures exposed to real environments.

Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study.

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.

Dry Dosage Forms of Add-Value Bioactive Phenolic Compounds by Supercritical CO2-Assisted Spray-Drying.

Every year, grapevine pruning produces huge amounts of residue, 90% of which are from vine shoots. These are a rich source of natural antioxidants, mostly phenolic compounds, which, when properly extracted, can give rise to added-value products. However, their lack of solubility in aqueous media and high susceptibility to thermal and oxidative degradation highly limit their bioavailability. Encapsulation in suitable carriers may have a positive impact on their bioavailability and bioactivity. Previous data on vine-shoot extraction have identified gallic acid (GA) and resveratrol (RSV) as the main phenolic compounds. In this work, model dry powder formulations (DPFs) of GA and RSV using hydroxypropyl cellulose (HPC) as carriers were developed using Supercritical CO2-Assisted Spray Drying (SASD). A 32 full factorial Design of Experiments investigated the solid and ethanol contents to ascertain process yield, particle size, span, and encapsulation efficiency. Amorphous powder yields above 60%, and encapsulation efficiencies up to 100% were achieved, representing excellent performances. SASD has proven to be an efficient encapsulation technique for these phenolic compounds, preserving their antioxidation potential after three months in storage with average EC50 values of 30.6 µg/mL for GA-DPFs and 149.4 µg/mL for RSV-DPF as assessed by the scavenging capacity of the DPPH radical.

Antibacterial and Antifungal Silver Nanoparticles with Tunable Size Embedded in Various Cellulose-Based Matrices.

The aim of this study was to synthesize silver nanoparticles (AgNPs) using cellulose derivatives and to evaluate their antimicrobial potential. As effective reducing and stabilizing agents for AgNPs, cellulose derivatives, such as hydroxypropyl cellulose (HPC), methylcellulose (MC), ethylcellulose (EC), and cellulose acetate (CA), were used. Their ability to reduce silver ions as well as the size of the resulting AgNPs were compared. The formation and stability of the reduced AgNPs in the solution were monitored using UV-Vis analysis. The size, morphology, and charge of the AgNPs were evaluated. We found that, when using cellulosic derivatives, AgNPs with sizes ranging from 17 to 89 nm and different stabilities were obtained. The parameters, such as size and ζ potential indicate the stability of AgNPs, with AgNPs-CA and AgNPs-HPC being considered more stable than AgNPs-EC and AgNPs-MC since they show higher ζ potential values. In addition, the AgNPs showed antimicrobial activity against all reference strains and clinical isolates. MIC values between 0.0312 and 0.125 mM had a bactericidal effect on both Gram-positive and Gram-negative bacteria. The fungicidal effect was obtained at a MIC value of 0.125 mM. These results may provide rational support in the design of medical gauze products, including gauze pads, rolls, and sponges.

Hydroxypropyl Cellulose Adhesives for Transfer Printing of Carbon Nanotubes and Metallic Nanostructures.

Transfer printing is one of the key nanofabrication techniques for the large-scale manufacturing of complex device architectures. It provides a cost-effective and high-throughput route for the integration of independently processed materials into spatially tailored architectures. Furthermore, this method enables the fabrication of flexible and curvilinear devices, paving the way for the fabrication of a new generation of technologies for optics, electronics, and biomedicine. In this work, hydroxypropyl cellulose (HPC) membranes are used as water soluble adhesives for transfer printing processes with improved performance and versatility compared to conventional silicone alternatives. The high-water solubility and excellent mechanical properties of HPC facilitate transfer printing with high yield for both metal and carbon nanotubes (CNTs) inks. In the case of metal inks, crack-free stripping of silver films and the simple fabrication of Moiré Plasmonic architectures of different geometries are demonstrated. Furthermore, HPC membranes are used to transfer print carbon nanotube films with different thicknesses and up to 77% transparency in the visible and near infrared region with potential applications as transparent conductive substrates. Finally, the use of prepatterned HPC membranes enables nanoscale patterning of CNT with feature resolution down to 1 µm.

Formulation, development and in vitro characterization of modified release tablets of capecitabine.

Objective: The main aim of this research work was to develop and evaluate cost effective modified release tablets of Capecitabine (CAP) without utilizing coating techniques.Methods: The tablets were prepared by non-aqueous wet granulation method. Hydroxypropyl cellulose (HPC) was used as an extended release matrix former and sodium alginate (SA) was used as sustained release agent due to its gel forming ability. 32 full factorial design was used to study the effect of the independent variables i.e. HPC and SA on dependent variables, in vitro drug release and swelling index. The physiochemical properties of the drug were analyzed by ultraviolet (UV), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (P-XRD). The formulated tablets were evaluated for hardness, thickness, weight variation, content uniformity, swelling index, and in vitro drug release study.Results: The FTIR and DSC studies confirmed that there was no any interaction between drug, polymers and excipients. Also from DSC and P-XRD studies it was clear that the crystalline nature of CAP was remain unchanged in the optimized formulation tablet. Formulation F8 retarded the drug release up to 24 h with the optimum concentration of the both the polymers.Conclusion: We have successfully developed the modified release tablets of CAP with the combination of diffusion and erosion controlled type of drug release mechanism.

Coacervate Thermoresponsive Polysaccharide Nanoparticles as Delivery System for Piroxicam.

Low water solubility frequently compromises the therapeutic efficacy of drugs and other biologically active molecules. Here, we report on coacervate polysaccharide nanoparticles (CPNs) that can transport and release a model hydrophobic drug, piroxicam, to the cells in response to changes in temperature. The proposed, temperature-responsive drug delivery system is based on ionic derivatives of natural polysaccharides-curdlan and hydroxypropyl cellulose. Curdlan was modified with trimethylammonium groups, while the anionic derivative of hydroxypropyl cellulose was obtained by the introduction of styrenesulfonate groups. Thermally responsive nanoparticles of spherical shape and average hydrodynamic diameter in the range of 250-300 nm were spontaneously formed in water from the obtained ionic polysaccharides as a result of the coacervation process. Their morphology was visualized using SEM and AFM. The size and the surface charge of the obtained objects could be tailored by adjusting the polycation/polyanion ratio. Piroxicam (PIX) was effectively entrapped inside the nanoparticles. The release profile of the drug from the CPNs-PIX was found to be temperature-dependent in the range relevant for biomedical applications.

Responsive Photonic Liquid Marbles.

Liquid marbles have potential to serve as mini-reactors for fabricating new materials, but this has been exploited little and mostly for conventional chemical reactions. Here, we uncover the unparalleled capability of liquid marbles to act as platforms for controlling the self-assembly of a bio-derived polymer, hydroxypropyl cellulose, into a cholesteric liquid crystalline phase showing structural coloration by Bragg reflection. By adjusting the cholesteric pitch via quantitative water extraction, we achieve liquid marbles that we can tailor for structural color anywhere in the visible range. Liquid marbles respond with color change that can be detected by eye, to changes in temperature, exposure to toxic chemicals and mechanical deformation. Our concept demonstrates the advantages of using liquid marbles as a miniature platform for controlling the liquid crystal self-assembly of bio-derived polymers, and their exploitation to fabricate sustainable, responsive soft photonic objects.

Dynamic rheology as a quantitative method for real-time tracking of excipient solvation in non-aqueous hydroxypropylcellulose topical gels.

This article describes a method to quantitatively track the solvation of HPC in a non-aqueous solvent system during topical gel manufacture. Where visual observation and microscopy could not establish a trend, straight-forward rheological profiling demonstrated a correlation between increased solvation of hydroxypropyl cellulose polymer (viscosity modifier) and decreased tan δ, indicating the formation of a viscoelastic gel network over time during processing. This correlation serves as a valuable tool for process optimization and HPC solvation tracking in non-aqueous topical gel formulations.

Montelukast nasal spray: formulation development and in vitro evaluation.

OBJECTIVES: The aim of this study was to evaluate potential development of montelukast sodium (MTS) as a nasal spray. MATERIALS AND METHODS: The formulations were prepared using hydroxypropyl cellulose (HPC) and carbomer 940 (C940). The prepared formulations were evaluated for clarity, pH, hydrodynamic size, zeta potential, viscosity, contact angle, surface tension, droplet size distribution, muco-adhesiveness, drug release, and stability. The suitable formulations were also assessed for their effects on nasal epithelial cells. RESULTS AND DISCUSSION: At room temperature (25 °C), the formulation containing 0.01% w/v C940 exhibited suitable viscosity and rheological properties. Spray droplets were in ranges of 10-40 µm, which are suitable for nasal administration. The works of adhesion of the formulations containing HPC or C940 were in the range of 0.8-4.0 and 0.2-27 µJ, respectively. In addition, the formulation containing 0.01% w/v C940 and the 0.5-15 µg/50 µL concentrations of MTS showed no signs of cytotoxicity and did not open the tight junction of nasal epithelial cells. CONCLUSION: The formulated MTS nasal spray is ideal for nasal administration for the treatment of allergic rhinitis. The formulation containing 0.01% w/v C940 had no toxicity nor alteration on the tight junction of nasal epithelial cells.

The Influence of Viscosity and Non-freezing Water Contents Bounded to Different Hydroxypropyl Celluloses (HPC) and Hydroxypropyl Methylcelluloses (HPMC) on Stability of Acetylsalicylic Acid.

The aim of the study was to examine the influence of non-freezing water (NFW) contents bound to hydroxypropyl methylcellulose (HPMC) or hydroxypropyl cellulose (HPC) binary mixtures using acetylsalicylic acid (ASA) as a model moisture-sensitive ingredient. Polysaccharides with significantly different physicochemical properties were mixed with acetylsalicylic acid at a ratio 1:1 (w/w). The measurements of NFW contents of hydrated samples were carried out using differential scanning calorimetry (DSC). In the method used, the dry mass normalized dependency of melting enthalpy (ΔH) and respective contents of water was found to be linear. NFW values were calculated after extrapolation ΔH to 0. For stability studies, HPC/ASA and HPMC/ASA mixtures were stored at 40°C and 75% RH for 5 weeks in the climatic chamber. The ASA hydrolysis was investigated using UV-Vis spectrophotometry. The amounts of NFW calculated for raw HPMC 3 cP and 100,000 cP were 0.49 and 0.42 g g-1, while for polymer and ASA mixtures, prepared from HPC type LF (126 cP) and MF (6300 cP) as well as from HPMC 3 cP and 100,000 cP were 0.23, 0.28 g g-1, 0.21 g g-1, and 0.33 g g-1 respectively. The measured NFW values were connected with appropriate concentrations of unhydrolyzed ASA.

Nifedipine di-matrix depot tablets prepared by compression coating for obtaining zero-order release.

Compression coating is a possible process for obtaining zero-order release. Nifedipine compression-coated (CC) di-matrix depot tablets were prepared from a single punch tablet press with low viscosity hydroxypropyl cellulose (HPC-L) as the inner polymer, and with middle viscosity hydroxypropyl cellulose (HPC-M), HPC-L and Eudragit RSPO as outer polymers. The release behavior and mechanisms in vitro of the final tablets were investigated, and gravimetric analysis was used to study the release mechanism. The fast release of the core depot and slow release of the outer depot with time formed total zero-order release. The results showed that the formulation presented ideal zero-order release at the weight ratio of nifedipine 3:5 (core: layer), the combination of HPC-L and HPC-M (56:25) in the outer depot, and with the core depot placed in the center. The CC tablets released to more than 95% in 24 h and fitted a zero-order model with the equation Mt/M∞ = 0.038t (R2 = 0.98555). In conclusion, zero-order release of nifedipine over 24 h could be achieved by applying polymer HPC-L and HPC-M with the compression coating technique.

Influence of processing methods on physico-mechanical properties of Ibuprofen/HPC-SSL formulation.

The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen and HPC-SSL. The powder blends, containing Ibuprofen and HPC-SSL in ratio of 9:0.5, were processed using melt granulation (MG) by hot melt extrusion (HME) and wet granulation (WG) by high shear mixer. Formulated granules and powder blends were compressed into round flat faced tablets using Riva Piccola tablet press. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) studies proved that granulation process did not significantly alter the crystallinity of Ibuprofen, however, particle density and flow properties were significantly improved. Scanning electron microscopy (SEM) and particle size analysis corroborate with the findings that the flow characteristics of granules from MG were relatively superior to other formulations. Formulations were investigated for out-of-die compaction behaviour using Heckel, Kawakita, and CTC profile analysis. Detailed examination revealed that all three formulations differed in particle size due to the granulation, thus conferring to different compaction behaviour. In WG and MG, granulation offered an increase in particle size resulting in high compressibility along with deformation at low compression pressure. This results into low yield pressure, low yield strength, and higher densification, as compared with dry blend. The current work provides an insight into factors affecting physical and mechanical properties tablets, which can facilitate the rational selection of suitable change in processing method instead of changing excipients.

Hydroxypropyl cellulose supplementation in vitrification solutions: a prospective study with donor oocytes.

PURPOSE: Hydroxypropyl cellulose (HPC), a polysaccharide that forms a viscous gel under low temperatures, is a promising substitute of the blood-derived macromolecules traditionally used in cryopreservation solutions. The performance of a protein-free, fully synthetic set of vitrification and warming solutions was assessed in a matched pair analysis with donor oocytes. METHODS: A prospective study including 219 donor MII oocytes was carried out, comparing the laboratory outcomes of oocytes vitrified with HPC-based solutions and their fresh counterparts. The primary performance endpoint was the fertilization rate. Secondary parameters assessed were embryo quality on days 2 and 3. RESULTS: 70/73 (95.9%) vitrified MII oocytes exhibited morphologic survival 2 h post-warming, with 49 (70.0%) presented normal fertilization, compared to 105 of 146 (71.9%) MII fresh oocytes. Similar embryo quality was observed in both groups. A total of 18 embryos implanted, out of 38 embryos transferred (47.3%), resulting in 13 newborns.