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Hye Su Kim,1 Ha-Kyoung Kwon,2 Dong Hoon Lee,1 Thao Nguyen Le,1 Hye-Jin Park,2 Moon Il Kim1 1Department of BioNano Technology, Gachon University, Seongnam, Gyeonggi 13120, Republic of Korea; 2Department of Food Science and Biotechnology, Gachon University, Seongnam, Gyeonggi 13120, Republic of KoreaCorrespondence: Moon Il KimDepartment of BioNano Technology, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam, Gyeonggi 13120, Republic of KoreaTel +82 31 750 8563Fax +82 31 750 4748Email moonil@gachon.ac.krIntroduction: Hair growth-promoting herbal extract mixtures (4HGF) exhibits significant anti-inflammatory activities relevant to promoting hair growth; however, its efficacy in patients with hair loss has been limited majorly due to its low penetration ability into hair follicles. Herein, we prepared hydrogels via dropwise addition of poly(γ-glutamic acid) (PGA) solution containing 4HGF into chitosan (CS) solution, resulting in quick formation of ∼400 nm-sized hydrogel particles through electrostatic interaction-derived ionic gelation with over 50% encapsulation efficiency of 4HGF (PGA-4HGF).Methods: The size and morphology of PGA-4HGF were characterized by TEM, SEM, and dynamic light scattering analyses. Encapsulation efficiency and loading capacity of 4HGF within PGA-4HGF, as well as in vitro release profiles were determined by simply measuring the characteristic absorbance of 4HGF. Penetrating efficiency of PGA-4HGF was evaluated by tracking the respective fluorescence through model porcine skin with confocal laser microscope system. By treating PGA-4HGF on telogenic mice and dermal papilla cells (DPCs), we evaluated the size of hair bulbs in mice, as well as morphological changes in DPCs.Results: Negligible and sustained release of entrapped 4HGF from the hydrogel nanoparticles were observed under acidic and physiological pH conditions, respectively, which is quite advantageous to control their release and prolong their hair growth-promoting effect. The hydrogel nanoparticles were penetrable through the porcine skin after incubation with or without shaking. After treating telogenic mice and DPCs with PGA-4HGF, we detected enlargement of hair bulbs and remarkable shape changes, respectively, thereby showing its potential in induction of hair growth.Conclusion: These results suggest that the hydrogel nanoparticle formulation developed in this study can be employed as a potential approach for the preservation of hair growth-promoting compounds, their delivery of into hair follicles, and enhancing hair growth.Keywords: hair growth, poly(γ-glutamic acid), chitosan, hydrogel nanoparticle, cosmeceutical

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung condition. It is characterized by disruption of gas exchange inside the alveoli, accumulation of protein edema, and an increase in lung stiffness. One major cause of ARDS is a lung infection, such as SARS-COV-2 infection. Lungs of ARDS patients need to be mechanically ventilated for airway reopening. Consequently, ventilation might damage delicate lung tissue leading to excess edema, known as ventilator-induced lung injury (VILI). Mortality of COVID-19 patients under VILI seems to be higher than non-COVID patients, necessitating effective preventative therapies. VILI occurs when small air bubbles form in the alveoli, injuring epithelial cells (EPC) due to shear stress. Nitric oxide (NO) inhalation was suggested as a therapy for ARDS, however, it was shown that it is not effective because of the extremely short half-life of NO. In this study, NO-releasing nanoparticles were produced and tested in an in vitro model, representing airways in the deep lung. Cellular injuries were quantified via fluorescent live/dead assay. Atomic force microscopy (AFM) was used to assess cell morphology. qRT-PCR was performed to assess the expression of inflammatory markers, specifically IL6 and CCL2. ELISA was performed to assess IL6 and confirm qRT-PCR results at the protein level. Finally, ROS levels were assessed in all groups. Here, we show that NO delivery via nanoparticles enhanced EPC survival and recovery, AFM measurements revealed that NO exposure affect cell morphology, while qRT-PCR demonstrated a significant downregulation in IL6 and CCL2 expression when treating the cells to NO both before and after shear exposure. ELISA results for IL6 confirmed qRT-PCR data. ROS experiment results support our findings from previous experiments. These findings demonstrate that NO-releasing nanoparticles can be used as an effective delivery approach of NO to deep lung to prevent/reduce ARDS associated inflammation and cell injuries. This information is particularly useful to treat severe ARDS due to COVID-19 infection. These nanoparticles will be useful when clinically administrated to COVID-19 patients to reduce the symptoms originating from lung distress.

[Display omitted] • A single Fe-site-containing hydrogel nanozyme was synthesized via an ionic gelation. • Fe-N sites function as active sites, yielding a significant peroxidase-like activity. • Foldable paper microfluidic device integrating two pH systems was developed. • Foldable device showed excellent analytical performances for detecting glucose. Peroxidase-mimicking nanozymes have been extensively studied, but their real utilization is limited by their working conditions limited to acidic pH, which makes it difficult to couple with oxidative enzymes operating at near-neutral pH. Here, we have developed a foldable paper microfluidic device that enables a highly convenient cascade reaction between peroxidase-mimicking nanozymes and oxidative enzymes to visually identify the target molecules. A single-atom iron-site-containing poly-γ-glutamic acid/chitosan hydrogel nanoparticle (PGA-Fe/CS NP) was developed, as a model peroxidase-like nanozyme, via rapid ionic gelation. Glucose oxidase (GOx) was used as a model oxidative enzyme. The paper device was constructed by simple wax-printing, including two parts with a foldable configuration: the first is for glucose oxidation under neutral pH and the second is for H 2 O 2 reduction to produce a colorimetric signal under acidic pH. By dropping the sample solution in the first part, the device allowed efficient glucose oxidation by the immobilized GOx at neutral pH. On merely folding the device, the produced H 2 O 2 from the glucose oxidation easily transfers to the second part of the device where PGA-Fe/CS NP was immobilized, inducing the peroxidase-like catalytic reaction at acidic pH. Using the foldable paper microfluidic device, the target glucose was successfully determined with excellent selectivity, sensitivity, stability, and reliability, using an image acquired by a smartphone. Since any oxidative enzymes could be incorporated into the device with the peroxidase-like PGA-Fe/CS NP, we expect that the foldable paper microfluidic device, which conveniently allows the cascade reaction under different pH environments, would be highly beneficial for the detection of various clinically important target molecules, thus laying the groundwork for future biosensing applications of nanozymes in point-of-care testing environments. [ABSTRACT FROM AUTHOR]

Nanoparticle evaluation within the pulmonary airspace has increasingly important implications for human health, with growing interest from drug delivery, environmental, and toxicology fields. While there have been widespread investigations of nanoparticle physiochemical properties following many routes of administration, nanoparticle behavior at the air-liquid interface (ALI) is less well-characterized. In this work, we fabricate two formulations of poly(ethylene)-glycol diacrylate (PEGDA)-based model nanoparticles to establish an in vitro workflow allowing evaluation of nanoparticle charge effects at the ALI. Both cationic and anionic PEGDA formulations were synthesized with similar hydrodynamic diameters around ~225 nm and low polydispersity, with expected surface charges corresponding with the respective functional co-monomer. We find that both formulations are readily nebulized from an aqueous suspension in a commercial Aeroneb ® Lab Nebulizer, but the aqueous delivery solution served to slightly increase the overall hydrodynamic and geometric size of the cationic particle formulation. However, nanoparticle loading at 50 μg/ml of either formulation did not influence the resultant aerosol diameter from the nebulizer. To assess aerosol delivery in vitro , we designed a 3D printed adapter capable of ensuring aerosol delivery to transwell 24-well culture plates. Nanoparticle uptake by macrophages was compared between traditional cell culture techniques and that of ALI-cultured macrophages following aerosol delivery. Cell viability was unaffected by nanoparticle delivery using either method. However, only traditional cell culture methods demonstrated significant uptake that was dependent on the nanoparticle surface charge. Concurrently, ALI culture resulted in lower metabolic activity of macrophages than those in traditional cell culture, leading to lower overall nanoparticle uptake at ALI. Overall, this work demonstrates that base-material similarities between both particle formulations provide an expected consistency in aerosol delivery regardless of the nanoparticle surface charge and provides an important workflow that enables a holistic evaluation of aerosolizable nanoparticles., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Biology and medicine have seen great advancements in the development of nanobiosensors capable of characterizing and quantifying biomolecules. This review reports a systematic study of the usefulness of hydrogel nanoparticles (HNPs) in the different steps of the electroanalytical process developed in electrochemical biosensing systems. We illustrate the advantages offered by HNPs in detection of analytes with representative recent examples that highlight the scientific interest in widening the use of HNPs in electrochemical biosensing methods. We review different types of HNP-based electrochemical biosensors, such as enzyme, protein, and nucleic acids, in terms of their sensing performance and their potential for future development. [ABSTRACT FROM AUTHOR]

Hydrogel nanoparticles of cross-linked polyvinylpyrrolidone (PVP-NP) (35–50 nm in diameter) containing fluoresceinated dextran (FITC-Dx) were encapsulated in reconstituted Sendai viral envelopes containing only the fusion (F) protein (F-virosomes11Process for Producing a Targeted Gene (1997) US Patent 5, 683, 866).). Incubation of these loaded F-virosomes with human hepatoblastoma cells (HepG2) in culture resulted in membrane-fusion-mediated delivery of NPs to the cell cytoplasm, as inferred from the ability of cells to internalize FITC-Dx loaded PVP-NP (PVPf-NP) in the presence of azide (an inhibitor of the endocytotic process). Introduction of PVPf-NP into the HepG2 cells was assured by selective accumulation of FITC fluorescence in the cytosolic compartment. The structural integrity of the internalized PVPf-NP was also confirmed by fluorescence microscopy and ultracentrifugation analysis. The potential usefulness of PVP-NP-mediated cytosolic release of water soluble drugs both in vitro and in vivo has been established for the first time. [Copyright &y& Elsevier]