Bioglass promotes wound healing by inhibiting endothelial cell pyroptosis through regulation of the connexin 43/reactive oxygen species (ROS) signaling pathway.

Bioactive glass (BG) has recently shown great promise in soft tissue repair, especially in wound healing; however, the underlying mechanism remains unclear. Pyroptosis is a novel type of programmed cell death that is involved in various traumatic injury diseases. Here, we hypothesized that BG may promote wound healing through suppression of pyroptosis. To test this scenario, we investigated the possible effect of BG on pyroptosis in wound healing both in vivo and in vitro. This study showed that BG can accelerate wound closure, granulation formation, collagen deposition, and angiogenesis. Moreover, western blot analysis and immunofluorescence staining revealed that BG inhibited the expression of pyroptosis-related proteins in vivo and in vitro. In addition, while BG regulated the expression of connexin43 (Cx43), it inhibited reactive oxygen species (ROS) production. Cx43 activation and inhibition experiments further indicate that BG inhibited pyroptosis in endothelial cells by decreasing Cx43 expression and ROS levels. Taken together, these studies suggest that BG promotes wound healing by inhibiting pyroptosis via Cx43/ROS signaling pathway.

Liquid Metal-Mediated Mechanochemical Polymerization.

Mechanically controlled polymerization that employs the mechanical energy to fabricate novel synthetic materials has attracted considerable interest. However, only a few examples have been achieved so far, owing to the limited choices of materials and strategies. Herein, a versatile, liquid metal (LM)-mediated mechanochemical polymerization method (LMMMP) is developed for the air-compatible, robust preparation of polymers in an aqueous solution. This method involves the simultaneous disruption of bulk LMs into micro- and nanodroplets and the combination of monomers into polymers during ultrasonic irradiation. The pristine and reactive LM surface continuously generated by ultrasound endows this polymerization method with excellent oxygen tolerance, high reaction rate, and the ability to produce polymers with high molecular weight from a wide variety of water-soluble monomers. Besides, LM droplets are readily reclaimed and reused for polymerization. The authors envision that the LMMMP promotes the utilization of mechanical energy for the synthesis of functional polymers, constitutes a novel fabrication approach for polymer-LM nanocomposites, and provides new insight into the design of LM-based platforms for polymerization.

Resveratrol-Loaded Dipalmitoylphosphatidylcholine Liposomal Large Porous Microparticle Inhalations for the Treatment of Bacterial Pneumonia Caused by Acinetobacter baumannii.

Background: Acinetobacter baumannii-mediated bacterial pneumonia is a common disease that is harmful to human health. Dipalmitoylphosphatidylcholine (DPPC) is the major lipid component of the pulmonary surfactant (PS) found in the alveolar space; the PS helps to keep surface tension low, which allows for improved oxygen delivery. Resveratrol (RE) is a phytoalexin found in plants that is released in response to injury or infection. The therapeutic effect of Re is limited due to its low solubility and bioavailability. In this study, we report pulmonary delivery of Re-loaded DPPC liposomal large porous microparticles (RDLPMs) for treatment of A. baumannii-induced pneumonia. Methods: Novel RDLPMs were prepared by rotary evaporation and a freeze-drying method in this study. RDLPMs were evaluated by the particle size, electric potential, in vitro release, and particle size distribution. A rat model of A. baumannii-mediated pneumonia was established and used for pharmacodynamic evaluations. Results: The Re-loaded DPPC liposomes (RDLs) consisted of Re/DPPC (1:3, mol/mol) and DPPC/cholesterol (3:1, w/w), with a hydration time of 15 minutes. The RDLs had a high encapsulation efficiency of 69.8% ± 1.6%, a mean size of 191.5 ± 4.5 nm, and a high zeta potential of 12.4 ± 1.5 mV. The RDLPMs were composed of mannitol/large porous microparticles/RDLs (1:4:2, w/w/w) and had a loading efficiency of 2.20% ± 0.24%. The RDLPMs had an aerodynamic diameter (2.73 ± 0.65 µm), a good fluidity (28.30° ± 6.13°), and demonstrated high lung deposition (fine particle fraction = 43.33%). Surprisingly, while penicillin showed better microbial inhibition than the RDLPMs and Re groups in vitro, the RDLPMs were more effective in vivo. Conclusion: The RDLPMs showed good powder properties for pulmonary delivery. The RDLPMs may inhibit the nuclear factor kappa-B pathway and downregulate the expression of cytokines downstream of tumor necrosis factor-α and interleukin-1ß. As well as, RDLPMs demonstrated some antibacterial properties against A. baumannii bacteria. Re, when delivered in RDLPMs as a dry powder inhaler, is a promising substitute for antibiotics in the treatment of A. baumannii pneumonia.

Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway.

Andrographolide (AG) is a chemical entity from traditional Chinese herbs and its oral pills have been applied to the treatment of respiratory inflammation. Here we report pulmonary delivery of liposomal AG dry powder inhalers (LADPIs) for treatment of Staphylococcus aureus-induced pneumonia. AG liposomes were prepared with the injection method and then freeze-dried for preparation of LADPIs. AG liposomes were small and stable with a mean size of 77.91nm and a zeta potential of -56.13mV. Liposomes were well recovered after re-hydration of LADPIs that were suitable for pulmonary delivery with a mass mean aerodynamic diameter (MMAD) of 4.87µm and a fine particle fraction (FPF) of 23.03%. However, the MMAD and FPF of AG powders were 10.14µm and 8.37%, respectively. The in vitro anti-S. aureus effects of AG powders and LADPIs were investigated, but were not found. They were intratracheally sprayed into the rat lungs for treatment of S. aureus pneumonia. Surprisingly, LADPIs showed a stronger anti-S. aureus pneumonic effect in vivo, than AG at a ten-fold dose or than an antibiotic, penicillin. LADPIs significantly decreased many pro-inflammatory cytokines including TNF-α, IL-1. Furthermore, the phosphorylation of IκB-α in the nuclear factor-κB (NF-κB) pathway was also remarkably inhibited. AG regulated the immune reaction to maintain the antibacterial effect while downregulating inflammatory response so that AG showed a strong effect on bacterial pneumonia. LADPIs are a promising pulmonary delivery medicine for the treatment of bacterial pneumonia.

Preparation of asiaticoside-loaded coaxially electrospinning nanofibers and their effect on deep partial-thickness burn injury.

Sodium alginate and chitosan were in favor of wound healing. However, the two polymers were not compatible in one formulation due to the electrostatic interaction. Coaxially electrospinning technology could make two or more noneletrospun polymers to be electrospun in independent core and shell layer. Asiaticoside-loaded coaxially electrospinning nanofibers of alginate, polyvinyl alcohol (PVA) and chitosan (alginate/PVA/chitosan) were prepared and evaluated. Morphologies and microstructure of nanofibers were observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Drug release in vitro of coaxial nanofibers was also evaluated. Deep partial-thickness burn injury were established and used to evaluate the improved healing effect of asiaticoside-loaded coaxial nanofibers. Drug-loaded coaxial nanofibers prepared with the optimized formulations and technologies had the obvious core-shell structure. Coaxial nanofibers showed faster drug release profiles in vitro and this facilitated wound healing. Its healing effect on rats with deep partial-thickness burn injury was also significant based on morphology, wound healing ratio, and pathological sections. Positive expression of vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), and proliferating cell nuclear antigen (PCNA), and down regulation of tumor necrosis factor (TNF) and interleukin-6 (IL-6) also validated the improved effect of wound healing. In general, the asiaticoside-loaded coaxial nanofibers had obvious core-shell structure with smooth surface and uniform diameter. Its healing effect on deep partial-thickness burn injury of rats was obvious. Asiaticoside-loaded coaxial nanofibers provide a novel promising option for treatment of deep partial-thickness burn injury.

Dimethyl silicone dry nanoemulsion inhalations: Formulation study and anti-acute lung injury effect.

Acute lung injury (ALI) is a severe disease, leading to death if not treated quickly. An emergency medicine is necessary for ALI therapy. Dimethyl silicone (DMS) is an effective agent to defoam the bubbles in the lung induced by ALI. However, DMS aerosols, a marketed formulation of DMS, affect environments and will be limited in the future. Here we firstly report a dry nanoemulsion inhalation for pulmonary delivery. Novel DMS dry nanoemulsion inhalations (DSNIs) were developed in this study. The optimal formulation of stable and homogenous DMS nanoemulsions (DSNs) was composed of Cremophor RH40/PEG 400/DMS (4:4:2, w/w/w) and water. The DSNs showed the tiny size of 19.8 nm, the zeta potential of -9.66 mV, and the low polydispersity index (PDI) of 0.37. The type of DSNs was identified as oil-in-water. The DSNs were added with mannitol followed by freeze-drying to obtain the DSNIs that were loose white powders, showed good fluidity, and were capable of rapid reconstitution to DSNs. The DSNs could adhere on the surfaces of lyophilized mannitol crystals. The aerodynamic diameter of DSNIs was 4.82 µm, suitable for pulmonary inhalation. The in vitro defoaming rate of DSNIs was 1.25 ml/s, much faster than those of the blank DSNIs, DMS, and DMS aerosols. The DSNIs showed significantly higher anti-ALI effect on the ALI rat models than the blank DSNIs and the DMS aerosols according to lung appearances, histological sections, and lung wet weight/dry weight ratios. The DSNIs are effective anti-ALI nanomedicines. The novel DMS formulation is a promising replacement of DMS aerosols.