Optimization of Interleukin-10 incorporation for dendritic cells embedded in Poly(ethylene glycol) hydrogels.

Translational research in biomaterials and immunoengineering is leading to the development of novel advanced therapeutics to treat diseases such as cancer, autoimmunity, and viral infections. Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)-4 arm maleimide (PEG-4MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin-10, IL-10, and cross-linked with a collagenase-degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease-relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis. The amount of IL-10 incorporated in the hydrogel was optimized to be 500 ng in vitro, based on immunological endpoints. At this concentration, DCs exhibited the best viability, most immunosuppressive phenotype, and protection against proinflammatory insult as compared with hydrogel-incorporated DCs with lower IL-10 loading amounts. Additionally, the effect of the degradability of the PEG-4MAL hydrogel on the release rate of incorporated IL-10 was assessed by varying the ratio of degradable peptides: VPM (degradable) and DTT (nondegradable) and measuring the IL-10 release rates. This IL-10-conjugated hydrogel delivery system for immunosuppressive DCs is set to be assessed for in vivo functionality as the immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype, which consequently enhances cell viability and optimizes the system's immunomodulatory functionality.

Effect of Poly(ethylene glycol) Configuration on Microbubble Pharmacokinetics.

Microbubbles (MBs) hold substantial promise for medical imaging and therapy; nonetheless, knowledge gaps persist between composition, structure, and in vivo performance, especially with respect to pharmacokinetics. Of particular interest is the role of the poly(ethylene glycol) (PEG) layer, which is thought to shield the MB against opsonization and rapid clearance but is also known to cause an antibody response upon multiple injections. The goal of this study was, therefore, to elucidate the role of the PEG layer in circulation persistence of MBs in the naïve animal (prior to an adaptive immune response). Here, we directly observe the number and size of individual MBs obtained from blood samples, unifying size and concentration into the microbubble volume dose (MVD) parameter. This approach enables direct evaluation of the pharmacokinetics of intact MBs, comprising both the lipid shell and gaseous core, rather than separately assessing the lipid or gas components. We examined the in vivo circulation persistence of 3 µm diameter phospholipid-coated MBs with three different mPEG2000 content: 2 mol % (mushroom), 5 mol % (intermediate), and 10 mol % (brush). MB size and concentration in the blood were evaluated by a hemocytometer analysis over 30 min following intravenous injections of 20 and 40 µL/kg MVD in Sprague-Dawley rats. Interestingly, pharmacokinetic analysis demonstrated that increasing PEG concentration on the MB surface resulted in faster clearance. This was evidenced by a 1.6-fold reduction in half-life and area under the curve (AUC) (p < 0.05) in the central compartment. Conversely, the AUC in the peripheral compartment increased with PEG density, suggesting enhanced MB trapping by the mononuclear phagocyte system. This was supported by an in vitro assay, which showed a significant rise in complement C3a activation with a higher PEG content. In conclusion, a minimal PEG concentration on the MB shell (mushroom configuration) was found to prolong circulation and mitigate immunogenicity.

Nonlinear Elastic Bottlebrush Polymer Hydrogels Modulate Actomyosin Mediated Protrusion Formation in Mesenchymal Stromal Cells.

The nonlinear elasticity of many tissue-specific extracellular matrices is difficult to recapitulate without the use of fibrous architectures, which couple strain-stiffening with stress relaxation. Herein, bottlebrush polymers are synthesized and crosslinked to form poly(ethylene glycol)-based hydrogels and used to study how strain-stiffening behavior affects human mesenchymal stromal cells (hMSCs). By tailoring the bottlebrush polymer length, the critical stress associated with the onset of network stiffening is systematically varied, and a unique protrusion-rich hMSC morphology emerges only at critical stresses within a biologically accessible stress regime. Local cell-matrix interactions are quantified using 3D traction force microscopy and small molecule inhibitors are used to identify cellular machinery that plays a critical role in hMSC mechanosensing of the engineered, strain-stiffening microenvironment. Collectively, this study demonstrates how covalently crosslinked bottlebrush polymer hydrogels can recapitulate strain-stiffening biomechanical cues at biologically relevant stresses and be used to probe how nonlinear elastic matrix properties regulate cellular processes. This article is protected by copyright. All rights reserved.

Improvement in Crystallization, Thermal, and Mechanical Properties of Flexible Poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) Bioplastic with Zinc Phenylphosphate.

Poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) shows promise for use in bioplastic applications due to its greater flexibility over PLLA. However, further research is needed to improve PLLA-PEG-PLLA's properties with appropriate fillers. This study employed zinc phenylphosphate (PPZn) as a multi-functional filler for PLLA-PEG-PLLA. The effects of PPZn addition on PLLA-PEG-PLLA characteristics, such as crystallization and thermal and mechanical properties, were investigated. There was good phase compatibility between the PPZn and PLLA-PEG-PLLA. The addition of PPZn improved PLLA-PEG-PLLA's crystallization properties, as evidenced by the disappearance of the cold crystallization temperature, an increase in the crystallinity, an increase in the crystallization temperature, and a decrease in the crystallization half-time. The PLLA-PEG-PLLA's thermal stability and heat resistance were enhanced by the addition of PPZn. The PPZn addition also enhanced the mechanical properties of the PLLA-PEG-PLLA, as demonstrated by the rise in ultimate tensile stress and Young's modulus. We can conclude that the PPZn has potential for use as a multi-functional filler for the PLLA-PEG-PLLA composite due to its nucleating-enhancing, thermal-stabilizing, and reinforcing ability.

Effect of Plasticization/Annealing on Thermal, Dynamic Mechanical, and Rheological Properties of Poly(Lactic Acid).

This study investigates the use of low molecular weight poly(ethylene glycol) (PEG) as a plasticizer for poly(lactic acid) (PLA). PLA/PEG blend films were prepared using the solvent casting method with varying mixing ratios. The films were analyzed using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and dynamic rheological analysis. The results indicate that the addition of PEG as a plasticizer affects the thermal and mechanical properties of the PLA/PEG blend films. The study found that the glass transition and cold crystallization temperatures decreased with increasing PEG content up to 20 wt%, while the crystallinity and crystallization rate increased. The blends with up to 20 wt% PEG were miscible, but phase separation occurred when the plasticizer content was increased to 30 wt%. Subsequently, amorphous samples of neat PLA and PLA plasticized with 10 wt% of PEG underwent annealing at various temperatures (Ta = 80-120 °C) for durations ta of 1 and 24 h. The samples were then analyzed using DSC and DMA. The addition of PEG to PLA altered the content of α' and α crystalline forms compared to neat PLA at a given (Ta; ta) and favored the formation of a mixture of α' and α crystals. The crystallinity achieved upon annealing increased with increasing Ta or ta and with the incorporation of PEG.

Reflections on a Copenhagen-Minneapolis Axis in Bioorganic Chemistry.

The international peptide community rejoiced when one of its most distinguished members, Morten Meldal of Denmark, shared the 2022 Nobel Prize in Chemistry. In fact, the regiospecific solid-phase "copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides" (CuACC) reaction-that formed the specific basis for Meldal's recognition-was reported first at the 17th American Peptide Symposium held in San Diego in June 2001. The present perspective outlines intertwining conceptual and experimental threads pursued concurrently in Copenhagen and Minneapolis, sometimes by the same individuals, that provided context for Meldal's breakthrough discovery. Major topics covered include orthogonality in chemistry; the dithiasuccinoyl (Dts) protecting group for amino groups in α-amino acids, carbohydrates, and monomers for peptide nucleic acids (PNA); and poly(ethylene glycol) (PEG)-based solid supports such as PEG-PS, PEGA, and CLEAR [and variations inspired by them] for solid-phase peptide synthesis (SPPS), solid-phase organic synthesis (SPOS), and combinatorial chemistry that can support biological assays in aqueous media.

Lignin-Based Hydrogels for the Delivery of Bioactive Chaga Mushroom Extract.

Lignin-poly(ethylene)glycol diglycidyl ether hydrogels were synthesized from lignin fractions readily extracted during the hot-water treatment of angiosperms: hardwoods, sugar maple and energy-crop willow, monocotyledons, grasses, miscanthus and agriculture residues, and wheat straw. These lignins represent a broad range of chemical structures and properties as a comparative analysis of their suitability to produce the hydrogels as a novel carrier of chaga-silver nanoparticles. The formation of hydrogels was assessed via attenuated total reflectance Fourier-transformed infrared spectroscopy. Then, the hydrogels were observed via scanning electron microscopy and evaluated for their free-absorbency capacity and moduli of compression. Furthermore, a hydrogel produced from kraft lignin and two commercial hydrogels was evaluated to benchmark the effectiveness of our hydrogels. Chaga extracts were prepared via the hot-water extraction of chaga mushroom, a method selected for its relatively higher yields and preserved antioxidizing activities. Hydrogels synthesized with lignins of monocotyledons, wheat straw, and miscanthus were found to be suitable carriers for chaga-silver nanoparticles due to their favorable absorption and release behaviors.

Tailoring the Degradation Time of Polycationic PEG-Based Hydrogels toward Dynamic Cell Culture Matrices.

Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to enhance in vitro cell culture conditions, although cell adhesion is often challenging when the cells are cultivated on the substrate surface. We herein demonstrate two approaches for the synthesis of polycationic PEG-based hydrogels which were modified to enhance cell-matrix interactions, to improve two-dimensional (2D) cell culture, and catalyze hydrolytic degradation. While the utilization of N,N-(bisacryloxyethyl) amine (BAA) as cross-linker for in situ gelation provides degradable scaffolds for dynamic cell culture, the incorporation of short segments of poly(N-(3-(dimethylamino)propyl)acrylamide) (PDMAPAam) provides high local cationic charge density leading to PEG-based hydrogels with high selectivity for fibroblastic cell lines. The adsorption of transforming growth factor (TGF-ß) into the hydrogels induced stimulation of fibrosis and thus the formation of collagen as a natural ECM compound. With this, these dynamic hydrogels enhance in vitro cell culture by providing a well-defined, artificial, and degradable matrix that stimulates cells to produce their own natural scaffold within a defined time frame.

Cu-MSNs and ZnO nanoparticles incorporated poly(ethylene glycol) diacrylate/sodium alginate double network hydrogel for simultaneous enhancement of osteogenic differentiation.

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.

Transition from active motion to anomalous diffusion for Bacillus subtilis confined in hydrogel matrices.

We investigate the motility of B. subtilis under different degrees of confinement induced by transparent porous hydrogels. The dynamical behavior of the bacteria at short times is linked to characteristic parameters describing the hydrogel porosity. Mean squared displacements (MSDs) reveal that the run-and-tumble dynamics of unconfined B. subtilis progressively turns into sub-diffusive motion with increasing confinement. Correspondingly, the median instantaneous velocity of bacteria decreases and becomes more narrowly distributed, while the reorientation rate increases and reaches a plateau value. Analyzing single-trajectories, we show that the average dynamical behavior is the result of complex displacements, in which active, diffusive and sub-diffusive segments coexist. For small and moderate confinements, the number of active segments reduces, while the diffusive and sub-diffusive segments increase. The alternation of sub-diffusion, diffusion and active motion along the same trajectory can be described as a hopping ad trapping motion, in which hopping events correspond to displacements with an instantaneous velocity exceeding the corresponding mean value along a trajectory. Different from previous observations, escape from local trapping occurs for B. subtilis through active runs but also diffusion. Interestingly, the contribution of diffusion is maximum at intermediate confinements. At sufficiently long times transport coefficients estimated from the experimental MSDs under different degrees of confinement can be reproduced using a recently proposed hopping and trapping model. Finally, we propose a quantitative relationship linking the median velocity of confined and unconfined bacteria through the characteristic confinement length of the hydrogel matrix. Our work provides new insights for the bacterial motility in complex media that mimic natural environments and are relevant to important problems like sterilization, water purification, biofilm formation, membrane permeation and bacteria separation.

Chitin nanofibrils assisted 3D printing all-chitin hydrogels for wound dressing.

The direct ink writing technique used in 3D printing technology is generally applied to designing biomedical hydrogels. Herein, we proposed a strategy for preparing all-chitin-based inks for wound dressing via direct ink writing technique. The ß-chitin nanofibers (MACNF) with a high aspect ratio were applied as a nanofiller to modulate the rheological properties of the alkaline dissolved chitin solution. The printing fidelity significantly depends on the MACNF introduction amount to the composite ink. 5-10 wt% MACNF ratio showed superior printing performance. The printed scaffold showed a uniform micron-sized pore structure and a woven network of nanofibers. Due to the good biocompatibility of chitin and the stereoscopic spatial skeleton, this scaffold showed excellent performance as a wound dressing, which can promote cell proliferation, collagen deposition and the angiogenesis of wounds, demonstrating its potential in biomedical applications. This approach successfully balanced the chitinous printability and biofunctions.

Tumor-specific cytolysis by peptide-conjugated echogenic polymer micelles.

Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate. Micelle formation using polymer amphiphiles in aqueous media and the subsequent carbon dioxide (CO2) gas generation from the micelles was confirmed. Their ability to target neuroblastoma was substantially enhanced by incorporating the rabies virus glycoprotein (RVG) peptide. RVG-modified gas-generating micelles significantly inhibited tumor growth in a tumor-bearing mouse model owing to CO2 gas generation within tumor cells and resultant cytolytic effects, showing minimal side effects. The development of multifunctional polymer micelles may offer a promising therapeutic approach for various diseases, including cancer.

Enhancing protein dynamics analysis with hydrophilic polyethylene glycol cross-linkers.

Cross-linkers play a critical role in capturing protein dynamics in chemical cross-linking mass spectrometry techniques. Various types of cross-linkers with different backbone features are widely used in the study of proteins. However, it is still not clear how the cross-linkers' backbone affect their own structure and their interactions with proteins. In this study, we systematically characterized and compared methylene backbone and polyethylene glycol (PEG) backbone cross-linkers in terms of capturing protein structure and dynamics. The results indicate the cross-linker with PEG backbone have a better ability to capture the inter-domain dynamics of calmodulin, adenylate kinase, maltodextrin binding protein and dual-specificity protein phosphatase. We further conducted quantum chemical calculations and all-atom molecular dynamics simulations to analyze thermodynamic and kinetic properties of PEG backbone and methylene backbone cross-linkers. Solution nuclear magnetic resonance was employed to validate the interaction interface between proteins and cross-linkers. Our findings suggest that the polarity distribution of PEG backbone enhances the accessibility of the cross-linker to the protein surface, facilitating the capture of sites located in dynamic regions. By comprehensively benchmarking with disuccinimidyl suberate (DSS)/bis-sulfosuccinimidyl-suberate(BS3), bis-succinimidyl-(PEG)2 revealed superior advantages in protein dynamic conformation analysis in vitro and in vivo, enabling the capture of a greater number of cross-linking sites and better modeling of protein dynamics. Furthermore, our study provides valuable guidance for the development and application of PEG backbone cross-linkers.

Improvement of cross-linked films based on chitosan/diepoxy-poly (ethylene glycol) incorporating trans-cinnamaldehyde essential oil: Preparation, properties, and application in banana storage.

In this study, development of bioactive coatings containing 1 % (w/v) chitosan (CS), 0.6 % (w/v) diepoxy-polyethylene glycol (PEG), and trans-cinnamaldehyde (CIN) was achieved. The physicochemical and biological properties of the coatings were investigated. The tensile strength, light transmission, water vapor permeability (WVP), and antibacterial properties were enhanced by the incorporation of CIN. The CIN-containing films appeared compact and rough, as observed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In addition, the quality attributes of the bananas were evaluated at room temperature for 24 days, and the results showed that the CS/PEG/CIN coating delayed the respiration peak, weight loss, sugar content loss, and maintained firmness, color, total soluble solids (TSS), titratable acid (TA), and the appearance of the bananas. Principal component analysis (PCA) revealed that the bioactive coating significantly affected the respiration rate and weight loss of bananas.

Bioactive Polyurethane-Poly(ethylene Glycol) Diacrylate Hydrogels for Applications in Tissue Engineering.

Polyurethanes (PUs) are a highly adaptable class of biomaterials that are among some of the most researched materials for various biomedical applications. However, engineered tissue scaffolds composed of PU have not found their way into clinical application, mainly due to the difficulty of balancing the control of material properties with the desired cellular response. A simple method for the synthesis of tunable bioactive poly(ethylene glycol) diacrylate (PEGDA) hydrogels containing photocurable PU is described. These hydrogels may be modified with PEGylated peptides or proteins to impart variable biological functions, and the mechanical properties of the hydrogels can be tuned based on the ratios of PU and PEGDA. Studies with human cells revealed that PU-PEG blended hydrogels support cell adhesion and viability when cell adhesion peptides are crosslinked within the hydrogel matrix. These hydrogels represent a unique and highly tailorable system for synthesizing PU-based synthetic extracellular matrices for tissue engineering applications.

Study the anticancer efficacy of doxorubicin-loaded redox-responsive chitosan-derived nanoparticles in the MDA-MB-231 cell line.

This study focuses on the design and evaluation of redox-responsive nanoparticles (NPs) by synthesizing disulfide-containing N-phthaloyl chitosan-SS-methoxy poly(ethylene glycol) (NPC-SS-mPEG) and incorporating the anti-cancer drug doxorubicin into the NPs. The structural features of NPC-SS-mPEG were investigated using FTIR, NMR, XRD, and TGA/DTA analysis. DLS and TEM analysis confirmed the particle size and morphology of the NPs. The stability of the NPs was measured with the presence and absence of glutathione (GSH) in buffers pH 5 and 7.4. Furthermore, the release of DOX from the NPs was studied in GSH (10 mM) containing/absent medium at pH 5 and pH 7.4 which mimics the intracellular environment with redox potential. The results indicated a significantly increased release of DOX in the GSH containing medium pH 5 (82.9 ± 2.1 %) and pH 7.4 (67.37 ± 0.88 %) compared to the GSH free pH 7.4 (29.99 ± 1.01 %) and pH 5 medium (56.56 ± 1.7 %) at 60 h. The cytotoxicity study in the MDA-MB-231 breast cancer cell line by MTT assay indicated higher toxicity of redox-responsive NPs to cancer cells than free DOX. In concurrence with the cytotoxicity assay, in-vitro fluorescence staining assays (AO/EB, Hoechst, ROS generation) also confirmed that NPs loaded with DOX induce higher toxicity to cancer cells than free DOX. Taken together, the overall results confirmed the superiority of the redox response-mediated release of DOX in effectively controlling cancer progression.

Overcoming limitations of conventional solvent exchange methods: Achieving monodisperse non-equilibrium polymer micelles through equilibration-nanoprecipitation (ENP).

Hypothesis Conventional solvent exchange formulation methods face limitations when trying to control the final non-equilibrium size properties of block copolymer micelles containing a strongly hydrophobicity and a rigid block because the solvent conditions are not well controlled during micelle formation. Therefore, using an alternative formulation method, named Equilibration-Nanoprecipitation (ENP), in which micelles are formed under uniform solvent conditions, will significantly reduce the final dispersity compared a conventional solvent exchange method. EXPERIMENTAL: Size properties of the final aqueous micelle dispersions formed from the ENP method and a conventional solvent exchange are measured using DLS. Also, a parallel modelling study is completed to predict the final size distributions using both methods. Findings The experimental results demonstrate the ENP method is effective producing non-equilibrium micelles with low dispersity below the monodisperse polydispersity index (PDI) cutoff for DLS while the conventional solvent exchange method leads to significantly greater dispersity. Also the experimental results highlight ENP can be used to tune the final size properties which cannot be done using methods which do not properly control the micelle formation conditions. Additionally, the modelling study supports the utility of the ENP approach for producing monodisperse dispersions of nonequilibrium polymer micelles.

Impact of Anti-PEG IgM Induced via the Topical Application of a Cosmetic Product Containing PEG Derivatives on the Antitumor Effects of PEGylated Liposomal Antitumor Drug Formulations in Mice.

Poly(ethylene glycol) (PEG) is used in many common products, such as cosmetics. PEG, however, is also used to covalently conjugate drug molecules, proteins, or nanocarriers, which is termed PEGylation, to serve as a shield against the natural immune system of the human body. Repeated administration of some PEGylated products, however, is known to induce anti-PEG antibodies. In addition, preexisting anti-PEG antibodies are now being detected in healthy individuals who have never received PEGylated therapeutics. Both treatment-induced and preexisting anti-PEG antibodies alter the pharmacokinetic properties, which can result in a subsequent reduction in the therapeutic efficacy of administered PEGylated therapeutics through the so-called accelerated blood clearance (ABC) phenomenon. Moreover, these anti-PEG antibodies are widely reported to be related to severe hypersensitivity reactions following the administration of PEGylated therapeutics, including COVID-19 vaccines. We recently reported that the topical application of a cosmetic product containing PEG derivatives induced anti-PEG immunoglobulin M (IgM) in a mouse model. Our finding indicates that the PEG derivatives in cosmetic products could be a major cause of the preexistence of anti-PEG antibodies in healthy individuals. In this study, therefore, the pharmacokinetics and therapeutic effects of Doxil (doxorubicin hydrochloride-loaded PEGylated liposomes) and oxaliplatin-loaded PEGylated liposomes (Liposomal l-OHP) were studied in mice. The anti-PEG IgM antibodies induced by the topical application of cosmetic products obviously accelerated the blood clearance of both PEGylated liposomal formulations. Moreover, in C26 tumor-bearing mice, the tumor growth suppressive effects of both Doxil and Liposomal l-OHP were significantly attenuated in the presence of anti-PEG IgM antibodies induced by the topical application of cosmetic products. These results confirm that the topical application of a cosmetic product containing PEG derivatives could produce preexisting anti-PEG antibodies that then affect the therapeutic efficacy of subsequent doses of PEGylated therapeutics.

Lipidated brush-PEG polymers as low molecular weight pulmonary drug delivery platforms.

OBJECTIVES: Nanomedicines are being actively developed as inhalable drug delivery systems. However, there is a distinct utility in developing smaller polymeric systems that can bind albumin in the lungs. We therefore examined the pulmonary pharmacokinetic behavior of a series of lipidated brush-PEG (5 kDa) polymers conjugated to 1C2, 1C12 lipid or 2C12 lipids. METHODS: The pulmonary pharmacokinetics, patterns of lung clearance and safety of polymers were examined in rats. Permeability through monolayers of primary human alveolar epithelia, small airway epithelia and lung microvascular endothelium were also investigated, along with lung mucus penetration and cell uptake. RESULTS: Polymers showed similar pulmonary pharmacokinetic behavior and patterns of lung clearance, irrespective of lipid molecular weight and albumin binding capacity, with up to 30% of the dose absorbed from the lungs over 24 h. 1C12-PEG showed the greatest safety in the lungs. Based on its larger size, 2C12-PEG also showed the lowest mucus and cell membrane permeability of the three polymers. While albumin had no significant effect on membrane transport, the cell uptake of C12-conjugated PEGs were increased in alveolar epithelial cells. CONCLUSION: Lipidated brush-PEG polymers composed of 1C12 lipid may provide a useful and novel alternative to large nanomaterials as inhalable drug delivery systems.

Mismatched Refractive Index Strategy for Fabricating Laser-Driven Wood Diffusers from Bulk Wood for Illumination Applications.

Laser-diode-based solid-state lighting is primarily used in state-of-the-art illumination systems. However, these systems rely on light-converting inorganic phosphors, which have low quantum efficiencies and complex manufacturing conditions. In this study, a mismatched refractive index strategy is proposed to directly convert natural bulk wood into a laser-driven wood diffuser using a simple delignification and polymer infiltration method. The resulting material has the potential to be used in laser-driven diffuse illumination applications. The optical performance of the laser-driven wood diffuser is optimized by changing the density of natural wood. The optimal coefficient of illuminance variation of the wood diffuser is as low as 17.7%, which is significantly lower than that of commercial diffusers. The illuminance uniformity is larger than 0.9, which is significantly higher than the ISO requirements for indoor workplace lighting. The laser damage threshold is 7.9 J cm-2, which is considerably higher than those of the substrates of commercially available phosphors. Furthermore, the optimized wood diffuser exhibits outstanding mechanical properties, excellent thermal stability, tolerance to harsh environmental conditions, and low speckle contrast. These results show that the laser-driven wood diffuser is a promising laser-color converter that is suitable for indoor, long-distance outdoor, undersea, and other high-luminance laser lighting applications.