Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

Co-delivery of Brinzolamide and Timolol from Micelles-laden Contact Lenses: In vitro and In Vivo Evaluation.

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.

Injectable hydrogel with antimicrobial and anti-inflammatory properties for postoperative tumor wound care.

Clinically, tumor removal surgery leaves irregularly shaped wounds that are susceptible to bacterial infection and further lead to excessive inflammation. Injectable hydrogel dressings with antimicrobial and anti-inflammatory properties have been recognized as an effective strategy to care for postoperative tumor wounds and prevent recurrence in recent years. In this work, we constructed a hydrogel network by ionic bonding interactions between quaternized chitosan (QCS) and epigallocatechin gallate (EGCG)-Zn complexes which were coordinated by EGCG and zinc ions. Because of the synergistic effect of QCS and EGCG-Zn, the hydrogel exhibited outstanding antimicrobial capacity (>99.9% inhibition), which could prevent infections caused byEscherichia coli and Staphylococcus aureus. In addition, the hydrogel was able to inhibit the growth of mice breast cancer cells (56.81% survival rate within 72 h) and reduce inflammation, which was attributed to the sustained release of EGCG. The results showed that the hydrogel was effective in inhibiting tumor recurrence and accelerating wound closure when applied to the postoperative tumor wounds. This study provided a simple and reliable strategy for postoperative tumor wound care using antimicrobial and anti-inflammatory injectable dressings, confirming their great potential in the field of postoperative wound dressings.

Sprayable Zwitterionic Antibacterial Hydrogel With High Mechanical Resilience and Robust Adhesion for Joint Wound Treatment.

Wound healing in movable parts, including the joints and neck, remains a critical challenge due to frequent motions and poor flexibility of dressings, which may lead to mismatching of mechanical properties and poor fitting between dressings and wounds; thus, increasing the risk of bacterial infection. This study proposes a sprayable zwitterionic antibacterial hydrogel with outstanding flexibility and desirable adhesion. This hydrogel precursor is fabricated by combining zwitterionic sulfobetaine methacrylate (SBMA) with poly(sulfobetaine methacrylate-co-dopamine methacrylamide)-modified silver nanoparticles (PSBDA@AgNPs) through robust electrostatic interactions. About 150 s of exposure to UV light, the SBMA monomer polymerizes to form PSB chains entangled with PSBDA@AgNPs, transformed into a stable and adhesion PSB-PSB@Ag hydrogel at the wound site. The resulting hydrogel has adhesive strength (15-38 kPa), large tensile strain (>400%), suitable shape adaptation, and excellent mechanical resilience. Moreover, the hydrogel displays pH-responsive behavior; the acidic microenvironment at the infected wound sites prompts the hydrogel to rapidly release AgNPs and kill bacteria. Further, the healing effect of the hydrogel is demonstrated on the rat neck skin wound, showing improved wound closing rate due to reduced inflammation and enhanced angiogenesis. Overall, the sprayable zwitterionic antibacterial hydrogel has significant potential to promote joint skin wound healing.

Contact lens as an emerging platform for ophthalmic drug delivery: A systematic review.

The number of people with eye diseases has increased with the use of electronics. However, the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons. Although many drug delivery systems have been developed to overcome these problems, they have certain limitations. In recent years, the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery. Hence, a review of the current state of research on drug delivery contact lenses has become crucial. This article reviews the key physical and chemical properties of drug-laden contact lenses, development and classification of contact lenses, and features of the commonly used materials. A review of the methods commonly used in current research to create contact lenses has also been presented. An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed. Overall, the review focuses on drug delivery methods using smart contact lenses, and predicts the future direction of research on contact lenses.

Gelatin Sponges with a Uniform Interoperable Pore Structure and Biodegradability for Liver Injury Hemostasis and Tissue Regeneration.

Developing a hemostatic sponge that can effectively control bleeding from visceral injuries while guiding in situ tissue regeneration in incompressible wounds remains a challenge. Most of the existing hemostatic sponges degrade slowly, are relatively single-functioning, and cannot cope with complex environments. Herein, a biodegradable rapidly hemostatic sponge (GPZ) was created by dual-dynamic-bond cross-linking among Zn2+, protocatechualdehyde (PA)-containing catechol and aldehyde groups, and gelatin. GPZ had a uniformly distributed interconnected pore structure with excellent fluid absorption. It could effectively absorb the oozing blood and increase the blood concentration while stimulating platelet activation and accelerating blood coagulation. Compared to commercial hemostats, GPZ treatment significantly accelerated hemostasis in the rat liver defect model (∼0.33 min, ≥50% reduction in the hemostatic time) and in the rabbit liver defect model (∼1.02 min, ≥60% reduction in the hemostatic time). Additionally, GPZ had excellent antibacterial and antioxidant properties that effectively protected the wound from infection and excessive inflammation. In the liver regeneration model, GPZ significantly increased the rate of hepatic tissue repair and promoted rapid functional recovery without complications and adverse reactions. Overall, we designed a simple and effective biodegradable rapid hemostatic sponge with good clinical translational potential for treating lethal incompressible bleeding and promoting wound healing.

The protective effects of propofol against renal ischemia-reperfusion injury are potentiated by norisoboldine treatment via inhibition of oxidative stress pathways.

Acute kidney injury (AKI) is a significant worldwide health problem. The protective effects of norisoboldine (NOR) against ischemia/reperfusion (I/R) induced renal injury in a rat model were evaluated. AKI was induced in rats by I/R. Animals were treated with 20 mg/kg/h propofol, intraperitoneally administered and 10 mg/kg NOR 30 min before inducing renal ischemia. Biomarkers of kidney function, including cytokines and oxidative stress parameters, were measured in serum. The serum levels of creatinine and blood urea nitrogen in propofol- and NOR-treated rats were lower compared to the untreated I/R group. Moreover, treatment with propofol or NOR, alone and in combination, decreased the levels of cytokines and oxidative stress in rats with kidney injury. In conclusion, this study suggested that treatment with NOR potentiated the nephroprotective effects of propofol in rats with I/R-induced renal injury by ameliorating oxidative stress and apoptosis pathway.

Dexmedetomidine targets miR-146a and participates in the progress of chronic obstructive pulmonary disease in vivo and in vitro.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease and the third leading cause of death in the world. Dexmedetomidine has been reported to effectively inhibit histamine-induced bronchoconstriction. However, the molecular mechanism of dexmedetomidine in COPD has not been found. OBJECTIVE: To explore the role and mechanism of dexmedetomidine in COPD, and to provide theoretical basis for clinical treatment of COPD. METHODS: The expression of miR-146a was regulated by mimics or inhibitor and the relative expression of apoptotic proteins p53, Bax and Bcl-2 in human bronchial epithelial 16HBE cells was determined by real-time PCR and Western blot. Dexmedetomidine was treated for 16HBE cells and alveolar epithelial type II cells (AEC2), the cell apoptosis was detected by TUNEL and Hoechst33342 staining. A COPD rat model was established by smoking to test the effects of dexmedetomidine on the progression of COPD. The levels of IL-6, IL-1ß and TNF-α in serum were measured by ELISA and the protein concentration of bronchoalveolar lavage fluid (BALF) was also detected in dexmedetomidine treated COPD rat model. RESULTS: miR-146a promoted 16HBE cell apoptosis and reduced cell proliferation. Additionally, dexmedetomidine was showed to reduce the 16HBEL cell apoptosis through reducing the expression of miR-146a. Moreover, dexmedetomidine regulated cell apoptosis and cell apoptosis through miR-146a in AEC2 cells. More importantly, dexmedetomidine attenuated the morphology and pathology of COPD rat model. CONCLUSION: Dexmedetomidine reduced 16HBE cells and AEC2 cell apoptosis and attenuated COPD by down-regulating miR-146a.

Confined Growth and Controlled Coalescence/Self-Removal of Condensate Microdrops on a Spatially Heterogeneously Patterned Superhydrophilic-Superhydrophobic Surface.

Manipulating condensate nucleation, growth, coalescence, and self-removal via bionic super-wettability surfaces has attracted intensive interest because of their significance in fundamental research and technological innovations, for example, water harvesting, power generation, air conditioning, and thermal management. However, it is still a challenge to simultaneously realize confined growth, coalescence, and self-ejection of condensate microdrops, which has not been reported to date. Here, we propose and demonstrate a type of new and more efficient coalescence/self-removal method based on spatially confined growth/coalescence/self-ejection of condensate microdrops, which can be realized using a rationally designed superhydrophobic surface with spatially heterogeneously patterned superhydrophilic microdots (SMDs). Exemplified by superhydrophobic closely packed zinc oxide nanoneedles with SMD patterns, we investigate how the geometric parameters of SMD patterns be designed to simultaneously realize the spatially confined growth/coalescence/self-ejection of patterned microdrops, which are rationalized via theoretical analyses.

Density Maximization of One-Step Electrodeposited Copper Nanocones and Dropwise Condensation Heat-Transfer Performance Evaluation.

Currently, it is still a great challenge to obtain copper-based high-efficient dropwise condensation heat transfer (CHT) interfaces via template-free electrodepositing technologies. Here, we report that the density of template-free electrodeposited copper nanocones can maximally reach 1.5 × 106/mm2 by the synergistic control of substrate surface roughness, poly(ethylene glycol) (PEG) molecular weight, and PEG concentration. After thiol modification, the densely packed copper nanocone samples can present low-adhesive superhydrophobicity and condensate microdrop self-jumping function at ambient environment. Condensation heat and mass transfer characterizations show that the CHT coefficient of copper surfaces can maximally enhance 98% for 20 °C vapor and 51% for 40 °C vapor by in situ growth of superhydrophobic densely packed copper nanocones. Although the dropwise condensation mode can change from the jumping mode to the mixed jumping and sweeping mode and the shedding-off mode along with the increase of surface subcooling and vapor temperature, the CHT performance of the nanosample is still superior to that of the contrast flat hydrophobic surface during the whole testing range of surface subcooling. As vapor temperature increases to 80 °C, the CHT performance of the nanosample is inferior to that of the contrast sample. The CHT enhancement under low-temperature vapor should be ascribed to the enhancement of small-drop mass transfer ability caused by low-adhesive superhydrophobicity nature of nanosample surfaces. Their performance degradation mainly results from increased drop-drop drag force along with the increase of surface subcooling and vapor temperature. In sharp contrast, the CHT deterioration under high-temperature vapor should be ascribed to larger drop-surface adhesion and drop-drop drag force. The former is caused by vapor penetration, whereas the latter is caused by the dramatically increased nucleation density and growth rate of condensates. These findings would help design and develop copper-based high-efficiency condensation heat transfer interfaces.

Microdrop-Assisted Microdomain Hydrophilicization of Superhydrophobic Surfaces for High-Efficiency Nucleation and Self-Removal of Condensate Microdrops.

Superhydrophobic-hydrophilic hybrid surfaces have attracted intensive interest because of their significant academic and commercial values. However, almost all reported microdomain hydrophilicization methods rely on costly micropatterning techniques that need special instruments. Here, we report a microdrop-assisted method for microdomain hydrophilicization of a low-adhesive superhydrophobic surface and demonstrate its utility in high-efficiency nucleation and self-removal of condensate microdrops. Micrometer-sized fogdrops containing polyvinyl alcohol molecules can be selectively captured by breath figures of superhydrophobic surfaces with specific sizes and spatial distributions and can be converted into desired hydrophilic microdomains after thermal evaporation. After exploring the influence of hydrophilic microdomains' distributions and sizes to surface wettability, adhesion, and condensation dynamics, we achieved an optimal hybrid surface, which possesses 240% average microdrop density, 387% microdrop self-removal rate, and 75% average microdrop diameter as compared to the contrast superhydrophobic surface with uniform chemistry nature. This method is dispensed with special equipment, easy to implement, very cheap, and eco-friendly, which would help develop other superhydrophobic-hydrophilic hybrid surfaces with different functions such as water harvesting, dehumidification, and heat exchange.

A Bioinspired, Highly Transparent Surface with Dry-Style Antifogging, Antifrosting, Antifouling, and Moisture Self-Cleaning Properties.

Transparent coatings with antireflection, antifogging, antifrosting, antifouling, and moisture self-cleaning properties can dramatically improve the efficiency and convenience of optical elements and thus are highly desirable for practical applications. Here, it is demonstrated that a bionic nanocone surface (BNS) fabricated by a facile, low-cost process consisting of template-assisted prepolymer curing followed by surface modification can possess the multiple functions listed above. The polymer coating firmly adheres to a glass substrate due to bonding agents. After SiO2 nanoparticle deposition and low-surface-energy fluorosilane modification, the coating shows low microdroplet adhesion. As a result, the as-prepared BNS exhibits a high transmittance when exposed to fog and good clarity even when the temperature decreases to -20 °C in a humid environment. Dipping the BNS into exemplified graphite powder has almost no influence on the transparency, and the BNS can realize self-cleaning of moisture when the surface is covered with a thick layer of man-made contaminants.

Corrigendum to "Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation".

[This corrects the article DOI: 10.1155/2015/167014.].

Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation.

Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2 significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2 induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p47(phox) and gp91(phox) protein expression, increases of the specific lipid peroxidation product 15-F2t-Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase and ß-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation.

Two NAC transcription factors from Caragana intermedia altered salt tolerance of the transgenic Arabidopsis.

BACKGROUND: Plants are continuously challenged by different environment stresses, and they vary widely in their adjustability. NAC (NAM, ATAF and CUC) transcription factors are known to be crucial in plants tolerance response to abiotic stresses, such as drought and salinity. ANAC019, ANAC055, and ANAC072, belong to the stress-NAC TFs, confer the Arabidopsis abiotic stress tolerance. RESULTS: Here we isolated two stress-responsive NACs, CiNAC3 and CiNAC4, from Caragana intermedia, which were induced by ABA and various abiotic stresses. Localization assays revealed that CiNAC3 and CiNAC4 localized in the nuclei, consistent with their roles as transcription factors. Histochemistry assay using Pro(CiNAC4)::GUS transgenic Arabidopsis showed that the expression of the GUS reporter was observed in many tissues of the transgenic plants, especially in the root vascular system. Overexpression of CiNAC3 and CiNAC4 reduced ABA sensitivity during seed germination, and enhanced salt tolerance of the transgenic Arabidopsis. CONCLUSIONS: We characterised CiNAC3 and CiNAC4 and found that they were induced by numerous abiotic stresses and ABA. GUS histochemical assay of CiNAC4 promoter suggested that root, flower and local damaged tissues were the strongest stained tissues. Overexpression assay revealed that CiNAC4 play essential roles not only in promoting lateral roots formation, but also in responding to salinity and ABA treatment of Arabidopsis.

Pivotal role of mast cell carboxypeptidase A in mediating protection against small intestinal ischemia-reperfusion injury in rats after ischemic preconditioning.

AIM OF THE STUDY: Mast cell (MC) degranulation contributes to the protection mediated by ischemic preconditioning (IPC); however, the precise mechanisms underlying this protection remain largely unknown. Mast cell carboxypeptidase A (MC-CPA) is released solely from MCs and plays a critical role in degrading toxins and endothelin 1 (ET-1). The present study sought to explore whether MC-CPA is involved in the process of IPC in a rodent model of small intestinal ischemia reperfusion (IIR) injury. MATERIALS AND METHODS: IIR injuries were induced in Sprague-Dawley rats by clamping the superior mesenteric artery for 60 min followed by reperfusion for 2 h. One cycle of 10 min intestinal ischemia and 10 min of reperfusion was used in the IPC group, and the MC stabilizer cromolyn sodium and MC potato carboxypeptidase inhibitor were administered before the start of IPC. At the end of experiment, intestine tissue was obtained for assays of the MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents and myeloperoxidase activities. Intestinal histologic injury scores and MC degranulation were assessed. Apoptosis indices and cleaved caspase- 3 protein expressions were quantified. RESULTS: IIR resulted in severe injury, as evidenced by significant increases in injury scores and MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents that were accompanied with concomitant elevations in cleaved caspase 3 expression, apoptosis indices, and myeloperoxidase activities. IPC induced a significant increase in MC-CPA3, induced MC degranulation, and attenuated IIR injury by downregulating IIR-induced biochemical changes, whereas cromolyn sodium and potato carboxypeptidase inhibitor abolished the IPC-mediated changes. CONCLUSIONS: These data suggest that IPC protected against IIR injury via the MC degranulation-mediated release of MC-CPA.