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Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O 2 ) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The standard way of isolating bypass vessels from surrounding structures during cerebral bypass surgery has been to use a rubber dam or neurosurgical patty. Here, the use of polyvinyl alcohol (PVA) sponges is described as a possible upgrade from these traditional bypass dams., Methods: PVA sponges were used to isolate bypass arteries from surrounding tissues during microvascular anastomosis in 25 patients undergoing bypass surgery at our institution., Results: There were no adverse events related to the use of PVA for microvascular anastomosis. PVA sponges offered some specific advantages when compared with rubber and cottonoid dams., Conclusions: Although preliminary, our experience using PVA sponges during microvascular anastomosis suggests some of their properties can facilitate cerebral bypass surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: After endoscopic endonasal reduction (EER) for medial blowout fracture (BOF), nasal packing may be necessary for sustaining the reduced orbital contents. This study aimed to introduce a new packing technique using Merocel in a glove finger.We retrospectively reviewed 131 patients with a mean age of 42.2 years (range, 13-80 years), who underwent EER for medial BOF, followed by a postoperative nasal packing of Merocel in a glove finger, between March 2016 and December 2019. Sex, age, side and cause of trauma, pre-operative diplopia and enophthalmos, duration from the occurrence of trauma to surgery, postoperative diplopia, enophthalmos, complications like sinusitis, and revision surgery were evaluated.The most common cause of injury was physical assault in 47 cases and a fall or slip event in 34. Pre-operatively 22 patients had diplopia and 1 patient had enophthalmos. Mean duration after trauma to the surgery was 13.2 days (range, 1-29 days). The mean operative time was 34.1 minutes (range, 10-70 minutes). Four weeks after operation, the nasal packing was removed at an outpatient clinic, with minimal pain, discomfort, and bleeding and no evidence of infection or inflammation. A computed tomography scan performed at 3 months postoperatively showed no re-bulging. The computed tomography image of 1 patient showed frontal sinus haziness; the patient had a headache and underwent endoscopic sinus surgery for symptomatic relief. Three patients had diplopia and 1 had enophthalmos at final follow-up. No other major postoperative complications were noted.Merocel in a glove finger packing technique proved itself to be safe and effective after EER for medial BOF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Topical agents typically remain in the wound site for time duration that are too short to effectively eradicate MRSA tradition formation of BZK that can be maintained within the wound site for longer time periods, should be more effective., Methods: The novel chitosan and poly (D,L-lactide-co-glycoside) nanoparticles loaded with benzalkonium bromide (BZK) were designed, for the promotion wound healing after MRSA infection. The physical characterization of these nanoparticles, as well as their antibacterial activity in vitro, release profile in simulated wound fluid, cell toxicity, anti-biofilm activity, and their ability to improve the skin wound healing in a mouse model were also studied., Results: These novel nanoparticles were found to have a significant antibacterial activity ( p <0.01), both in vitro and in vivo test. The stronger anti-biofilm ability of the nanoparticles to inhibit the formation of bacterial biofilms, at a concentration of 3.33 μg/mL, and clear existing bacterial biofilms, at a concentration of 5 mg/mL, compared with its water solution. In addition, significant damage to bacterial cell walls also was found, providing insight into the mechanism of antibacterial activity., Conclusion: Taken together, these results demonstrated the ability of BZK-loaded nanoparticles in the promotion of skin wound healing with MRSA infection. The current findings open a new avenue for nanomedicine development and future clinical applications in the treatment of wounds., Competing Interests: The authors declared that there is no conflict of interest., (© 2021 Wu et al.)

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC 0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

High mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases. The aim of this study was to establish animal model of acute rhinosinusitis (ARS), and determine whether ethyl pyruvate (EP) attenuate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in ARS animals. Thirty-six Sprague Dawley (SD) rat were used as follows: six normal controls without intervention (group 1); thirty rats were used for establishment of ARS rats model by nasal insertion of Merocel sponge, and model rats without any treatments (group 2), treated with nasal drops of sterile saline (group 3), 10 μl EP (group 4), and 20 μl EP (group 5), twice a day for 5 days, respectively. Bacterial culture was done regularly and the main bacterial strains were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. HMGB1 expression in sinonasal mucosa was detected by immunohistochemistry and RT-PCR. Serum levels of HMGB1, IL-6, and TNF-α were determined by ELISA. Data from 29 of 36 rats that had completed research were analyzed. Bacterial colony formation unit (CFU) of nasal secretion was significantly higher in each group of ARS rats compared with controls (p < 0.001). ARS rats treated with EP had only slightly decreased CFU, but significantly attenuated inflammatory response of sinonasal mucosa and decreased HMGB1 expression compared to those treated with saline alone (p < 0.001). Serum levels of HMGB1, IL-6 and TNF-α were significantly higher in ARS rats compared to controls, and decreased by EP treatments (p < 0.001). Nasal sponge packing led to acute inflammatory response of nasal sinus in rats, and increased the expression of HMGB1, IL-6, and TNF-α. Nasal drops with EP could attenuate the inflammation of sinonasal mucosa through inhibiting the expression of HMGB1, IL-6 and TNF-α in ARS rats.

Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.

This study targets to develop curcumin-loaded polyvinyl alcohol/cellulose nanocrystals (PVA/CNCs) membrane as localized delivery system for breast/liver cancer. A novel strategy was developed for enhancing encapsulation capacity and maximizing therapeutic efficiency of curcumin-loaded PVA/CNCs membranes. Membranes were prepared by solution-casting method using citric acid as crosslinker. SEM revealed that PVA/CNCs ratio (80:20) was chosen as the optimum for loading curcumin. FT-IR indicated that, curcumin was incorporated into PVA/CNCs in amorphous-phase via intermolecular hydrogen bond between curcumin and membrane components. Curcumin showed biphasic-release through burst-release of 41% of curcumin during the first hour, followed by sustained-release of 70% and 94% during 24 h and 48 h, respectively. In vitro cytotoxicity of PVA/CNCs/Curcumin membrane exhibited a selective inhibition proliferation of breast and liver cancer cells in a concentration-dependent without any toxic effect on normal cells. At high concentration (8 mg/ml) of PVA/CNCs/Curcumin, reduced viability to 35% and 7% of MCF-7 and Huh-7 cells, respectively; meanwhile high HFB-4 normal cell viability ≥80% was investigated. Antimicrobial activity of PVA/CNCs/Curcumin was investigated by multi-drug-resistant strains, and MIC values. PVA/CNCs/Curcumin membranes with concentration (40 mg/ml) showed broad-spectrum antimicrobial activities, thus inhibited ~96-99% of microbial growth. PVA/CNCs/Curcumin membranes could be as promised anti-infective biomaterials for breast and liver cancer wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol., Materials and Methods: A total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300-500 μm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits., Results: Nine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed., Conclusions: TASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Microwave assisted synthesis of graft copolymer of polymeric blend of Fenugreek seed mucilage (FSM)-Polyvinyl alcohol (PVA) with acrylamide (AM) was done by free radical polymerization using ammonium per sulfate (APS) as initiator. Varying amount of AM and APS was used to optimize the best grade based on highest percentage grafting efficiency and investigated with intrinsic viscosity measurement, Fourier Transformation infrared spectroscopy (FTIR), 13 C NMR spectra, X-ray diffraction, elemental analysis, Thermogravimetric analysis, Scanning electron microscopy. The results of intrinsic viscosity indicate that the optimized sample GF4 has longer chain length than in comparison to the native mucilage and thus exhibits more swelling tendencies and thus can be used as very good controlled release matrix system. The thermal analysis and X-ray indicates that GF4 is more stable and possess more amorphous properties than the native FSM. The NMR and FT-IR studies reveal that in GF4 there is prominent presence of amide and the hydroxyl groups indicating that grafting mechanism has efficiently taken place. Histological studies & SEM image for optimized grade implanted on animals revealed sufficient tissue growth and exhibited biodegradability proving the material to be biocompatible and suitable to be used as tissue engineered scaffolds. The controlled release behavior of the optimized polymeric system GF4 was evidenced by 95% release of loaded drug Enalapril maleate for 16 h. Graphical abstract.

In this study, we developed ticagrelor-dispersed nanosuspension (TCG-NSP) to enhance the dissolution and oral bioavailability of ticagrelor (TCG) through a statistical design approach. TCG, a reversible P2Y 12 receptor antagonist, is classified as a biopharmaceutics classification system (BCS) class IV drug with low solubility and permeability, resulting in low oral bioavailability. Nanosuspension (NSP) is an efficient pharmaceutical technique for overcoming the disadvantages. First, we optimized TCG-NSP consisting of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl alcohol (PVA), which exhibited homogeneously dispersed TCG particle (233 nm) and low precipitation (3%). Characterization studies demonstrated that TCG-NSP provided amorphous TCG particles and supersaturation effect, resulting in higher dissolution than a commercial product. In addition, everted gut sac and pharmacokinetic studies confirmed that TCG-NSP improved the gastrointestinal permeation of TCG by 2.8-fold compared to commercial product, thereby enhancing the oral bioavailability (2.2-fold). These results suggested that TCG-NSP could be successfully used as an efficient pharmaceutical formulation to achieve the enhanced dissolution and oral bioavailability of TCG., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: To explore the relationship of embolic particle size used in prostate artery embolisation (PAE) to patient outcomes., Materials and Methods: A systematic review of PubMed, EMBASE, and the Cochrane database was undertaken to identify all existing studies using PAE for benign prostatic hyperplasia (BPH). Inclusion criteria included prospective studies reporting baseline and 12-month International Prostate Symptom Score (IPSS) and particle size. Exclusion criteria were overlapping studies, commentaries, abstracts, and letters. Data extraction from eligible studies included the size of embolic particle, particle material, and baseline and 12-month values for the following patient outcomes: IPSS, IPSS quality of life, urinary flow rate (Q-max), prostate volume, prostate specific antigen, and post-void residual volume. A meta-regression analysis was then undertaken to examine the relationship of particle size to patient outcome measures., Results: Six studies with a total of 687 patients were identified. Meta-regression analysis demonstrated particle size as a statistically significant (p<0.001) moderator of 12-month IPSS change following PAE. No statistically significant relationships were identified with other patient outcome measures., Conclusion: Smaller embolic particle size is associated with a greater reduction in IPSS following PAE., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To compare the efficacy of right portal vein embolization using ethylene vinyl alcohol (EVOH-PVE) compared to other embolic agents and surgical right portal vein ligation (PVL). Material and methods: Patients with right sided liver malignancies scheduled for extensive surgery and receiving induction of liver hypertrophy via right portal vein embolization/ligature between 2010-2016 were retrospectively evaluated. Treatments included were ethylene vinyl alcohol copolymer (Onyx®, EVOH-PVE), ethiodized oil (Lipiodol ® , Lipiodol/PVA-PVE), polyvinyl alcohol (PVA-PVE) or surgical ligature (PVL). Liver segments S2/3 were used to assess hypertrophy. Primary outcome was future liver remnant growth in ml/day. Results: Forty-one patients were included (EVOH-PVE n =  11; Lipiodol/PVA-PVE n =  10; PVA-PVE n =  8; PVL n =  12), the majority presenting with cholangiocarcinoma and colorectal metastases ( n =  11; n =  27). Pre-interventional liver volumes were comparable ( p =  .095). Liver hypertrophy was successfully induced in all but one patient receiving Lipiodol/PVA-PVE. Liver segment S2/3 growth was largest for EVOH-PVE (5.38 ml/d) followed by PVA-PVE (2.5 ml/d), with significantly higher growth rates than PVL (1.24 ml/d; p <  .001; p =  .007). No significant difference was evident for Lipiodol/PVA-PVE (1.43 ml/d, p =  .809). Conclusions: Portal vein embolization using EVOH demonstrates fastest S2/3 growth rates compared to other embolic agents and PVL, potentially due to its permanent portal vein embolization and induction of hepatic inflammation.

Novel nanomaterials have been developed for antimicrobial and wound healing applications. Here, we report the preparation of a polyvinyl alcohol/chitosan (PVA/CS) nanofiber with carboxymethyl chitosan nanoparticles (CMCS-OH30 NPs) encapsulating the antibacterial peptide OH-CATH30 (OH-30). The PVA/CS nanofibers containing OH-30 NPs (NP-30-NFs) obtained via electrospinning could achieve a secondary embedded OH-30. The effect of NP-30-NFs on the release of OH-30 was investigated through high-performance liquid chromatography. The antibacterial activities of NP-30-NFs against Escherichia coli and Staphylococcus aureus were studied by bacterial plate counting. NP-30-NFs containing different concentrations of NPs were applied to mouse skin wounds to determine their effectiveness in promoting wound healing. Results showed that NP-30-NFs exhibited antibacterial properties and promoted skin wound healing., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: A randomized controlled trial was held to compare nonabsorbable packs to steroid-eluting absorbable stents as middle meatal spacers after endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS)., Methods: CRS patients were randomly assigned to receive either nonabsorbable Merocel packs wrapped in non-latex glove material (packing type A) or Propel steroid eluting stents (packing type B). Twenty-two-item Sino-Nasal Outcome Test (SNOT-22) scores were collected preoperatively and postoperatively during the initial 4 debridements up to 3 months. Recording of the nasal endoscopy was also collected during all postoperative visits. In addition, Lund-Kennedy scores and middle turbinate lateralization scores, using a new visual analogue scale, were compared between the 2 types of packing., Results: Forty CRS patients were prospectively enrolled in this institutional review board (IRB)-approved study. Patients with packing type A had significantly lower middle turbinate lateralization scores at their first (∼10 days) postoperative visit (p = 0.02 and p = 0.04, for left and right sides, respectively). This difference disappeared by later postoperative visits (from 20 days to 3 months). Overall, patients receiving packing type A had significant lower SNOT-22 scores at 20 days postsurgery (p = 0.05). This difference also disappeared at 1 and 3 months postoperation. There were no statistically significant differences in Lund-Kennedy scores., Conclusion: In this study, nonabsorbable packing materials showed significant superior middle meatal spacing capacities as evidenced by greater middle turbinate medialization capability at the first postoperative visit. Additionally, patients with this type of packing saw improvements in their SNOT-22 scores at the 20-day postoperative visit. This study showed that there was no significant improvement in postoperative outcomes with drug-eluting stents when compared to nonabsorbable packing., (© 2019 ARS-AAOA, LLC.)

Lappaconitine (LA), a potent analgesic drug extracted from the root of natural aconitum species, has been clinically used for years because of its effectiveness and non-addictive properties. However, it is mainly limited in oral and intravenous administration in the form of Lappaconitine Hydrobromide (LAH). In this work, Lappaconitine trifluoroacetate (LAF), a new derivative of LA, was successfully obtained by introducing organofluorine group to LA. This new compound had a lower toxicity (LD 50 of 21.14 mg·kg -1 ), improved analgesic effect and longer half-life (T 1/2 of 2.24 h) when compared with LAH. Moreover, in vitro transdermal permeation (J ss of 206.82 μg·cm -2 ·h -1 ) of LAF was 30.54% higher than that of LAH, means that LAF can be conveniently used for transdermal drug delivery (TDD). Therefore, drug membranes with PVA solution (10 wt%) containing LAF in various amounts were fabricated by electrospinning. The in vitro release tests confirmed that up to 81.43% of LAF in the PVA/LAF nanofibrous membranes could be released in 72 h, accompanied by significant analgesic effect when compared with the blank control group. In conclusion, the prepared LAF-loaded membrane is a novel formulation for the treatment of chronic and long-term pain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Malignant glioblastoma (GB) treatment consists of resection surgery followed by radiotherapy and chemotherapy (CT). Despite several implications, such as systemic toxicity and low efficacy, CT continues to be used for GB therapy. Aiming to overcome the blood-brain barrier (BBB) limitations, one of the most promising approaches is the use of drug delivery systems (DDS) to treat the cancer cells in situ. Dacarbazine (DTIC) is an antitumor agent that has limited application given its high toxicity to healthy cells. However, it is effective against GB recurrent cells. In this study, DTIC polymeric nanofibers (NF) were successfully prepared, characterized and its in vitro anticancer efficacy was determined. This system demonstrated high drug loading of 83.9 ± 6.5%, good stability and mechanical properties and sustained drug release, improved in tumor pH (6.8). This controlled release prolonged the uptake of GB improving DTIC antitumor effects such as DNA damage and cell death by apoptosis. Molecular dynamics simulations revealed that DTIC interacts with PVA, possibly explaining the controlled release of the drug. Therefore, DTIC NF brain-implants show great potential as a promising drug delivery system for GB therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nerve wrapping improves neurorrhaphy outcomes in case of peripheral nerve injuries (PNIs). The aim of this preclinical study was to assess the efficacy of two novel biodegradable wraps made of a synthetic 1% oxidized polyvinyl alcohol (OxPVA) and a natural leukocyte-fibrin-platelet membrane (LFPm) versus the commercial product NeuraWrap. After rats sciatic nerve transection and neurorrhaphy, the wraps were implanted and compared for functional outcome, by sciatic function index assessment; structural characteristics, by histological/immunohistochemical analysis; ultrastructural features, by transmission electron microscopy. Moreover, a morphometric study was also performed and collagen distribution was observed by Second Harmonic Generation microscopy. After 12 weeks from implantation, all wraps assured nerve function recovery; no scar tissue/neuromas were visible at dissection. LFPm wraps were completely resorbed, while residues of OxPVA and NeuraWrap were observed. In all groups, biocompatibility was confirmed by the absence of significant inflammatory infiltrate. According to histological/immunohistochemical analysis and morphometric findings, OxPVA and LFPm wraps were both effective in preserving nerve integrity. These results assess that bioengineered OxPVA and LFPm wraps successfully guarantee favorable lesion recovery after PNI/neurorrhaphy and, in future, may be considered an interesting alternative to the commercial NeuraWrap.

Background: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases., Methods: Eight days after subcapsular implantation of 5 × 10 5 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses., Results: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid., Conclusion: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.

The purpose of this study was to explore the influence of stabilizer type and concentration on the properties of spray dried nanosuspension-in-microparticles (NS-in-MPs) for inhalation. Taking resveratrol (RES) as a Biopharmaceutical Classification System II (BCS II) model drug, the RES containing nanosuspensions were fabricated by high pressure homogenization method with different stabilizers including sodium dodecyl sulphate (SDS), sodium alginate (SA), chitosan (CS) and polyvinyl alcohol (PVA). Then, the nanosuspensions were spray dried with mannitol to obtain inhalable NS-in-MPs. The particle size, morphology, drug existing state, in vitro aerodynamic performance, in vitro release behavior, lung retention and pharmacokinetic behaviors were characterized. It was found that the morphology, lung deposition as well as in vitro drug release from the microparticles were significantly influenced by stabilizer type, with 1% PVA as stabilizer presenting the highest fine particle fraction (FPF). Meanwhile, taking PVA as an example, it was found stabilizer concentration could alter morphology and flowability of the microparticles, and the FPF value decreased with the increase of stabilizer concentration. Further drug retention and in vivo pharmacokinetic studies demonstrated that the positively charged stabilizer CS could facilitate drug retention and minimize drug expose to the systemic circulation. In conclusion, the deposition and lung retention behavior of NS-in-MPs could be well tuned by selecting different type or concentration of stabilizers, which could facilitate local lung diseases therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The discomfort and complications have always been problems for nasal packing materials. This study provided a new nasal packing material called high expansion degradable cotton (HEDC)., Methods: Nasal endoscopic surgery was used to establish a dog model of nasal bleeding, and wound surfaces were filled with Merocel, Nasopore and HEDC, respectively. Intraoperative and postoperative bleeding of 24 h was calculated. We evaluate the absorbability score, adhesion score, infection sore and nasal mucosal epithelium in postoperative 3, 7, 14 and 28 days. HE staining and electron microscopy were used to evaluate the recovery of nasal mucosa., Results: There was no significant difference in nasal bleeding between HEDC, Merocel and Nasopore. Nasal endoscopic examination revealed HEDC absorbability of score, adhesion score, infection score were significantly lower than Merocel and Nasopore. The epithelialization time of HEDC was significantly shorter than that of Merocel and Nasopore. HE staining showed that HEDC and Nasopore could significantly reduce scar hyperplasia on the wound surface. The results of electron microscopy suggested that HEDC could protect the edge cilia of the wound., Conclusion: HEDC could be used as new choice for hemostasis after nasal endoscopic surgery, which could reduce nasal epithelialization time, and protect wound edge cilia.

Electrospinning is a micrometric or nanometric scale fiber manufacturing technique with structural factors such as greater contact surface and pore size that allows the incorporation of biological agents in its structure, increasing their potential for medical applications. Due to the conditions required for the electrospinning process, such as high voltage, in the present work, the evaluation of the antimicrobial activity of schizophyllan-based membranes elaborated by electrospinning at 20 kV incorporated with Hamamelis virginiana was carried out against Staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa. The schizophyllan production was 1.97 gL -1 from strain Schizophyllum commune ScIBL1. The conditions for the process were standardized for voltage, feed flow, and the distance from the injector to the collector. Membranes with smooth-edged fibers, diameter of 819 nm without the presence of beads were obtained. However, it was found that the membranes lost antimicrobial activity against all the microorganisms evaluated, whereas, bioassays showed that null toxicity was presented.

Study Objective: The primary objective of this study is to compare the effectiveness of 3 treatment protocols to stop anterior epistaxis: classic compression, nasal packing, and local application of tranexamic acid. It also aims to determine the frequency of rebleeding after each of these protocols., Methods: This single-center, prospective, randomized controlled study was conducted with patients who had spontaneous anterior epistaxis. The study compared the effect of 3 treatment options, tranexamic acid with compression but without nasal packing, nasal packing (Merocel), and simple nasal external compression, on the primary outcome of stopping anterior epistaxis bleeding within 15 minutes., Results: Among the 135 patients enrolled, the median age was 60 years (interquartile range 25% to 75%: 48 to 72 years) and 70 patients (51.9%) were women. The success rate in the compression with tranexamic acid group was 91.1% (41 of 45 patients); in the nasal packing group, 93.3% (42 of 45 patients); and in the compression with saline solution group, 71.1% (32 of 45 patients). There was an overall statistically significant difference among the 3 treatment groups but no significant difference in pairwise comparison between the compression with tranexamic acid and nasal packing groups. In regard to no rebleeding within 24 hours, the study found rates of 86.7% in the tranexamic acid group, 74% in the nasal packing group, and 60% in the compression with saline solution group., Conclusion: Applying external compression after administering tranexamic acid through the nostrils by atomizer stops bleeding as effectively as anterior nasal packing using Merocel. In addition, the tranexamic acid approach is superior to Merocel in terms of decreasing rebleeding rates., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Post-operative adhesion is a common cause of several complications including intestinal obstruction, chronic pelvic pain and/or infertility. Adhesions are fibrous bands that result from the inflammatory reactions due to peritoneum damage. The current study focused on designing an effective anti-inflammatory loaded barrier for the prevention of post-operative adhesions. The proposed method is based on the use of polyvinyl alcohol (PVA), cryobarrier loaded with Ibuprofen (Ibu). Anti-adhesive Ibu-cryobarriers were prepared in different forms, and subjected to in-vitro evaluation comprising; drug release rate, maximum swelling index, morphological examination using scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FTIR) and mechanical properties. Optimized cryobarriers were further investigated for their in-vivo effectiveness in preventing post-operative adhesions in female Sprague-Dawley rats. All formulations showed appropriate physical and morphological characteristics, in-vitro controlled sustained drug release profiles during a period of seven days with acceptable maximum swelling index. Invivo, all cryobarriers were equivalent to each other concerning serum or tissue parameter. However, morphological and histopathological evaluations revealed that both xerocryogel and lyophilized cryofilms are more effective than the cryogel in prevention of post-operative peritoneal adhesions. The current study showed the possibility of preparing drug loaded cryobarriers using simple technique with an effective in vivo post-operative adhesion prevention., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Different substances are combined to compensate for each other's drawbacks and create an appropriate biomaterial. A novel Polyvinyl alcohol (PVA)/chitosan (CS) porous hydrogel was designed and applied to the treatment of osteochondral defects., Methods: Hydrogels of various PVA/CS ratios were tested for physiochemical and mechanical properties in addition to cytotoxicity and biocompatibility. The hydrogels with the best PVA/CS ratio were used in the animal study. Osteochondral defects were created at the articular cartilage of 18 rabbits. They were assigned to different groups randomly (n = 6 per group): the osteochondral defect only group (control group), the osteochondral defect treated with hydrogel group (HG group), and the osteochondral defect treated with hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) group (HG-BMSCs group). The cartilage was collected for macro-observation and histological evaluation at 12 weeks after surgery., Results: The Hydrogel with PVA/CS ratio of 6:4 exhibited the best mechanical properties; it also showed stable physical and chemical properties with porosity and over 90% water content. Furthermore, it demonstrated no cytotoxicity and was able to promote cell proliferation. The HG-BMSCs group achieved the best cartilage healing., Conclusions: The novel PVA/CS porous composite hydrogel could be a good candidate for a tissue engineering material in cartilage repair.

Haemosuccus pancreaticus (HP) is an uncommon cause of upper gastrointestinal (GI) bleeding, most often intermittent, making it difficult to diagnose, becoming fatal. It usually occurs in patients with chronic pancreatitis and is caused by the rupture of a visceral aneurysm within the main pancreatic duct. The association between pseudoaneurysm formation and pancreatitis is well established. Pseudoaneurysm occurs in 3.5%-10% of pancreatitis cases and its rupture is a rare but life-threatening complication of chronic pancreatitis occurring in 6%-8% of patients with pseudocysts and corresponds to less than 1% of cases of GI bleeding.Its diagnosis is challenging, given the intermittent nature of bleeding. Angiographic therapy is considered the first-choice treatment, especially in patients who are stable haemodynamically. We present a case of embolisation of inferior pancreaticoduodenal branches with polyvinyl alcohol microparticles in the treatment of HP., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: In this study, we aimed to investigate whether there was a significant prognostic difference between single and multiple cervical dilations when inducing second-trimester abortion., Methods: We conducted a retrospective review of 238 pregnant women who underwent termination of pregnancy at 12-21 weeks of gestation at Osaka University Hospital in Osaka, Japan, between January 2010 and May 2018. Termination of pregnancy was performed by vaginal administration of 1 mg gemeprost every 3 h for up to five doses per day after uterine cervical dilation using lamicel., Results: The women were categorized into two groups: 191 women had a delivery time of <24 h, whereas 47 had delivery times >24 h. Contrasting the groups, there were significant differences with regard to numbers of primiparas (88 [46.1%] and 32 [68.1%], respectively) and lamicel exchanges ± SD (1.9 ± 0.67 for <24 h and 2.4 ± 0.87 for >24 h, respectively). Additionally, we compared the prognosis of primiparas that received just a single lamicel with that of primiparas that had ≥2 exchanged, but no significant differences were noted in the number of patients with a delivery time of >24 h and the number of used gemeprost., Conclusion: Primipara is a risk factor for delayed delivery time of induced abortion. However, increasing the number of exchanged lamicel did not significantly reduce the delivery time; therefore, it should be performed as minimally as possible., (© 2019 Japan Society of Obstetrics and Gynecology.)

Chitosan like natural polymers have been widely used in burn wound management. Novel low molecular weight chitosan-PVA soft membranes have been studied for antibacterial and wound healing properties. The effectiveness of antibacterial activity was carried against bacterial pathogens while wound healing nature of chitosan was conducted in second degree burns on rabbits as model animal. Rabbits were divided into three groups; control untreated, treated with commercial Fusidic acid (Fu-A) cream and chitosan-PVA membranes. Low molecular weight chitosan showed significant antibacterial property towards bacterial pathogens. Wound healing experiments on second degree burn exhibited chitosan as significant wound healing agent for wound dressings. In morphological studies, normal growth of epidermis was observed and chitosan exhibited more effective for wound healing. Morphological studies also showed that chitosan wound dressings accelerated the granule and fibrous connective tissues formation. Physical characteristics of chitosan-PVA membranes were evaluated by water uptake capacity, SEM analysis, mechanical and water barrier studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the safety and efficacy of bronchial artery embolization (BAE) in patients with primary lung cancer-related hemoptysis and to identify factors associated with hemoptysis-free survival., Methods: Data from 84 patients with primary lung cancer (non-small cell [n = 74] and small cell [n = 10]) who underwent BAE from 1997 to 2018 for the management of hemoptysis were retrospectively reviewed. Of these, 53 patients had stage IV lung cancer. The hemoptysis volume prior to initial BAE was trivial (blood-tinged sputum) in 21 patients, moderate (< 300 mL per 24 hours) in 34 patients, and massive (> 300 mL per 24 hours) in 29 patients., Results: Technical success, defined as the ability to selectively embolize the abnormal vessel, was achieved in 83 patients (98.8%), and clinical success was achieved in 69 (82.1%) patients. Polyvinyl alcohol particles were used to embolize in 51 patients, gelfoam in 15 patients, and gelfoam plus microcoils in 17 patients. Hemoptysis recurred in 20 patients (23.8%) during follow-up. The median hemoptysis-free survival and overall survival periods were both 61 days. In the clinical-success and clinical-failure groups, the median overall survival period was 99 and 9 days, respectively (P < .001). In multivariable analysis, massive hemoptysis (P = .012) and cavitary lung mass (P = .019) were predictive factors for shortened hemoptysis-free survival., Conclusions: BAE is a safe and effective approach to control hemoptysis, although the prognosis in primary lung cancer patients presenting with hemoptysis is generally poor. Massive hemoptysis and cavitary lung mass are significant predictors of shortened hemoptysis-free survival., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare different imaging techniques (volume perfusion CT, cone-beam CT, and dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel MR imaging) in evaluation of transarterial chemoembolization of hepatocellular carcinoma (HCC) using radiopaque drug-eluting embolics (DEE)., Materials and Methods: MR imaging and CT phantom investigation of radiopaque DEE was performed. In the clinical portion of the study, 13 patients (22 HCCs) were prospectively enrolled. All patients underwent cross-sectional imaging before and after transarterial chemoembolization using 100-300 μm radiopaque DEE. Qualitative assessment of images using a Likert scale was performed., Results: In the phantom study, CT-related beam-hardening artifacts were markedly visible at a concentration of 12% (v/v) radiopaque DEE; MR imaging demonstrated no significant detectable signal intensity changes. Imaging obtained before transarterial chemoembolization showed no significant difference regarding tumor depiction. Visualization of tumor feeding arteries was significantly improved with volume perfusion CT (P < .001) and cone-beam CT (P = .002) compared with MR imaging. Radiopaque DEE led to significant decrease in tumor depiction (P = .001) and significant increase of beam-hardening artifacts (P = .012) using volume perfusion CT before versus after transarterial chemoembolization. Greater residual arterial tumor enhancement was detected with MR imaging (10 HCCs) compared with volume perfusion CT (8 HCCs) and cone-beam CT (6 HCCs)., Conclusions: Using radiopaque DEE, the imaging modalities provided comparable early treatment assessment. In HCCs with dense accumulation of radiopaque DEE, treatment assessment using volume perfusion CT or cone-beam CT may be impaired owing to resulting beam-hardening artifacts and contrast stasis. Dynamic contrast-enhanced MR imaging may add value in detection of residual arterial tumor enhancement., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Bariatric surgery is currently the only effective treatment with long-lasting results to treat severe obesity., Objectives: We performed a pilot study to evaluate the feasibility, safety and efficacy of percutaneous distal embolization of the left gastric artery (LGA) using a transradial approach., Methods and Results: We recruited seven severely obese male patients (mean age 48 ± 7 years) referred for diagnostic coronary angiography. Mean baseline weight was 160 ± 27 kg and body mass index was of 52 ± 8 kg/m 2 . We successfully injected 300-500 μm polyvinyl alcohol particles using 5Fr catheters and all distal LGA were occluded at the end of procedures. Mean procedure duration was 24 ± 13 min and mean fluoroscopy time was 10 ± 5 min. Six patients reported mild transient epigastric discomfort, which resolved with proton pump inhibitors. At 2 months, the average weight loss was of 7 ± 6 kg (median loss: -10 kg [-2, -11]), 6 ± 12 kg (median loss: -9 kg [-16, +4]) at 6 months and 13 ± 17 kg (median loss: -11 kg [0, -25]) up to 12 months after index procedures., Conclusion: Percutaneous transradial LGA embolization appears to be a promising technique to reduce the obesity burden. Randomized trials are required to further delineate the risk/benefit ratio, potential clinical indications and long term results., (© 2018 Wiley Periodicals, Inc.)

Purpose: To evaluate the safety and efficacy of prostatic artery embolization (PAE) using the combination of 50-μm and 100-μm polyvinyl alcohol (PVA) particles versus 100-μm PVA particles alone in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH)., Materials and Methods: Over a 5-year period, 120 patients treated with PAE for lower urinary tract symptoms (LUTS) secondary to BPH were randomized to undergo embolization with 50-μm plus 100-μm PVA particles (group A) or 100-μm PVA particles alone (group B). Mean follow-up time was 34 months (range, 12-57 mo). There were no differences between groups regarding baseline data. Primary outcome measurements included change in International Prostate Symptom Score (IPSS) and incidence of adverse events. Secondary outcome measurements included procedure-associated pain, prostate ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and changes over time in quality of life (QOL) questionnaire, peak urinary flow rate (Q max ), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific antigen (PSA) level, and International Index of Erectile Function (IIEF) were evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS temporally but increased IPSS ≥ 8 or QOL score ≥ 3 or decrease in Q max to < 7 mL/s., Results: Mean follow-up periods were 35 months ± 22 in group A and 33 months ± 25 in group B (P = .629). No differences between groups regarding procedural details, pain scores, or adverse events were noted (P > .05). At 24 month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7 ± 12.5 vs 14.8 ± 13.5), QOL score (3.7 ± 1.5 vs 2.4 ± 1.8), Q max (10.5 mL ± 9.5 vs 6.8 mL ± 5.0), PVR (92.0 mL ± 75.0 vs 60.0 mL ± 55.0), and PV (37.0 mL ± 19.5 vs 25.5 mL ± 15.0) compared with patients in group B (P < .05 for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% ± 20 in group A and 41% ± 25 in group B (P = .021); mean PSA levels at 24 hour after PAE were 92.5 ng/mL ± 55.0 in group A and 77.5 ng/mL ± 45.0 in group B (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P = .024). The mean IIEF-5 was not significantly different from baseline in either group., Conclusions: PAE with 50-μm plus 100-μm PVA particles resulted in greater improvement in clinical and imaging outcomes and no significant differences in adverse events compared with 100-μm PVA particles alone., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

With the non-selective vasodilating action, short half-life and first-pass metabolism of sildenafil (SC), local application in the lung for pulmonary arterial hypertension is of high demand. Although several nanosystems have been lately investigated, nanostructured lipid carriers (NLCs) give promises of potential safety, biodegradability and controlled drug release. In the current study, NLCs comprising either precirol, stearic acid or beeswax as solid lipid in presence of oleic acid as liquid lipid and PVA or poloxamer as emulsifier were prepared. Optimized NLCs (200-268 nm in size) were appraised versus SLNs both in vitro and in vivo. Precirol/PVA-based SLNs and NLCs ensued high entrapment efficiencies (EE > 95%) and controlled release behaviour over 6 h even though NLCs showed higher release profile. Stability studies at 4 °C indicated potential colloidal and entrapment stability over 3 months. Interestingly, NLCs demonstrated efficient nebulization, low interaction with mucin and higher viability of A549 cells (3-fold increase in IC 50 relative to SLNs) providing good aptitudes for pulmonary application. In vivo administration of free SC in rats revealed localized intra-alveolar bleeding, presumably related to excessive vasodilatation. Meanwhile, the nanoencapsulated drug confirmed normal lung parenchyma with minimal incidence of bleeding. Inspiring results highlight the potential of sildenafil-laden nanostructured lipid carriers as pulmonary drug delivery system., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Some marine creatures like jellyfish have gel-like bodies consisting mostly of water (above 95 wt%). Yet, their gel-like bodies still show quite good mechanical properties and can respond to external stimuli. Artificial hydrogels with very high water content are generally extremely weak, and hence their practical applications are strongly limited. Inspired by jellyfish, tough and biocompatible poly(vinyl alcohol)/sodium polyacrylate (PVA/PAANa) hydrogels with very high equilibrium water content (98.23-99.58 wt%) are developed. The equilibrium swollen PVA/PAANa hydrogels show good mechanical properties, with elastic modulus, tensile strength, and elongation up to 0.046 MPa, 0.14 MPa, and 206%, respectively, very close to those of jellyfish mesoglea. Moreover, the PVA/PAANa hydrogels can respond to external multi-stimuli distinctly, such as metal cations, pH, and salts. Very impressively, the PVA/PAANa hydrogel can easily distinguish tap water from deionized water, and its detection limit of metal cations can be as low as 10 -4  mol L -1 . Cell cytotoxicity tests and in vivo biocompatibility tests prove that the PVA/PAANa hydrogels have excellent biocompatibility. The tough, stimuli-responsive, and biocompatible hydrogels with very high water content may find a variety of practical applications in load-bearing biomaterials, detection, sensors, and agricultural fields., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Apocynin (APO), a specific NADPH oxidase inhibitor, is a bioactive phytochemical that exhibits versatile pharmacological activities. However, its rapid elimination and poor bioavailability represent great challenges to pharmaceutical scientists. Accordingly, novel chitosan-based APO-loaded solid lipid nanoparticles (CS,APO - loaded SLN S ) were developed to address such obstacles. A full 2 4 factorial design of experiment approach was employed to evaluate the individual and combined effect of critical process parameters namely; the amount of glycerol tristearate (GTS, X A ) and sucrose mono palmitate (SMP, X B ) as well as the concentration of chitosan (CS, X C ) and polyvinyl alcohol (PVA, X D ), on different critical quality attributes. Full characterization and extensive in vitro-in vivo evaluations of the optimized SLNs formula were conducted. The optimized formula, with core (CS,APO) and shell (PVA), has enhanced oral and intravenous bioavailability in rats as clearly verified when compared with APO solution. Probably, PVA hindered opsonization intravenously and SLNs reduced pre-systemic effect. In conclusion, the novel chitosan-based SLNs system would open new vistas in potentiating the bioavailability and sustaining the effect of APO and other bioactive phytochemicals with comparable properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Drug development is a long process which requires careful evaluation of the drug substance (active pharmaceutical ingredient, API), drug product (tablet, capsule etc.) and the bioperformance (both pre-clinical and clinical) before testing the efficacy of the final dosage form. The earliest assessment of a new drug substance requires an understanding of the safety and clinical performance (Phase 1) wherein faster processes (like on-site formulation strategy) have been set in place for quick clinical read-outs. One key gap that exists in this early assessment is the ability to evaluate modified release drug products. Here, an additive manufacturing approach is used to prepare polyvinyl alcohol (PVA) capsule shells using 3D printing (3DP), where the shells can be filled with either a solid or a liquid vehicle containing the API. In this work we demonstrate how we can delay the release of the API from the printed capsules allowing us to evaluate regional absorption in pre-clinical studies. By using 3DP, a new method to provide a series of release profiles is demonstrated, where the induction time of a delayed burst release is controlled by the wall thicknesses of printed capsules. New hanging baskets were also designed and 3D printed for the dissolution tests to better understand the rupturing of these capsules in an USP 2 dissolution apparatus. By controlling the wall thickness of the capsule, the induction time of drug release can be controlled from 12 to 198 min. This wide range of induction times demonstrated with this 3DP strategy is not currently available in a commercially available oral drug product form. Varying the induction times to the drug release to interrogate different regions of the GI tract is exhibited in vivo (beagle dogs) and initial analysis suggested a good in vitro/in vivo relationship (IVIVR)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An antibacterial and environmentally friendly chitosan (CS) /polyvinyl alcohol (PVA) blend membrane for air filtration was prepared via nonsolvent induced phase separation (NIPS) method. The chemical structure, thermal behavior, morphology, mechanical property and surface charge of the resultant CS/PVA membranes were characterized. Results showed that CS and PVA were miscible due to the intermolecular hydrogen bond between them. The blend membrane obtained from over 20 wt.% CS concentration exhibited a gradient interconnected porous structure without skin layer. The air filtration efficiency and pressure drop obtained from CS/PVA membrane with 30 wt.% CS concentration and the thickness of 37 μm under a face velocity of 5.3 cm s -1 were 95.59% and 633.5 Pa, respectively. The performance of air filtration obtained is mainly attributed to the direct interception of membrane surface. Further, the antibacterial rate of the blend membrane was up to 94.8% for E. coli and 91.3% for S. aureus., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Skin injuries are frequently encountered in daily life, but deep wounds often poorly self-heal and do not recover completely. In this study, we propose a novel skin patch that combines antibiotic, cell-derived extracellular matrix (ECM) and biocompatible polyvinyl alcohol (PVA) hydrogel. Methods: Decellularized human lung fibroblast-derived matrix (hFDM) was prepared on tissue culture plate (TCP) and PVA solution was then poured onto it. After a freeze-thaw process, PVA was peeled off from TCP along with hFDM tightly anchored to PVA. Subsequently, ciprofloxacin (Cipro)-incorporated PVA/hFDM (PVA/Cipro/hFDM) was fabricated via diffusion-based drug loading. Results: In vitro analyses of PVA/Cipro/hFDM show little cytotoxicity of ciprofloxacin, stability of hFDM, rich fibronectin in hFDM, and good cell attachment, respectively. In addition, hFDM proved to be beneficial in promoting cell migration of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs) using transwell inserts. The antibacterial drug Cipro was very effective in suppressing colony growth of gram-negative and -positive bacteria as identified via an inhibition zone assay. For animal study, infected wound models in BALB/c mice were prepared and four test groups (control, PVA, PVA/Cipro, PVA/Cipro/hFDM) were administered separately and their effect on wound healing was examined for up to 21 days. The results support that Cipro successfully reduced bacterial infection and thus encouraged faster wound closure. Further analysis using histology and immunofluorescence revealed that the most advanced skin regeneration was achieved with PVA/Cipro/hFDM, as assessed via re-epithelialization, collagen texture and distribution in the epidermis, and skin adnexa (i.e., glands and hair follicles) regeneration in the dermis. Conclusion: This work demonstrates that our skin patch successfully consolidates the regenerative potential of ECM and the antibacterial activity of Cipro for advanced wound healing., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

In this study, we prepared a series of silver sulfadiazine (AgSD)-loaded polyvinyl alcohol (PVA) hydrogels via electron beam (e-beam) irradiation. Our objective was to explore the influence of e-beam irradiation on the chemical structure and crystallinity of AgSD and the antibacterial properties of AgSD/PVA hydrogels. Prior to irradiation, we mixed AgSD in PVA solution in 2 forms, either suspended in water (WS) or dissolved in ammonia solution (AS). We noted that nano silver was released from AgSD/PVA-AS hydrogels immersed in deionized water, while it would not happen in AgSD/PVA-WS hydrogels. Both kinds of AgSD/PVA hydrogels exhibited good antibacterial activities against gram-negative Escherichia coli and gram-positive Staphylococcus aureus. And their antibacterial activity was not obviously affected by different dosages of e-beam irradiation. Moreover, the antibacterial activity of the AgSD/PVA-WS hydrogels was stronger than that of AgSD/PVA-AS. Accordingly, the cell cytotoxicity of the AgSD/PVA-WS hydrogels was higher than that of AgSD/PVA-AS. Our study results reveal that e-beam irradiation of PVA solution with dispersed AgSD is a simple and efficient way to prepare AgSD/PVA hydrogels, which might be an ideal antibacterial wound dressing., (Copyright © 2018. Published by Elsevier Inc.)

In this work, Eu-containing poly (vinyl acetate) and poly (vinyl alcohol) are made into triple physical cross-linked hydrogels. The hydrogels exhibit good tensile strength, ultrahigh toughness, excellent compressive recovery and identifiability. The superior mechanical properties of the hydrogels originate from the synergetic interactions of hydrogen bonding, molecular crystals, and hydrophobic interactions. The hydrogels are identifiable due to the introduction of the Eu(iii) organic complex [Eu(DBM)2(Phen)MA] into vinyl acetate and the identifiability of the hydrogel proves the uniformity of two types of polymers (Eu-PVAc and PVA) in the hydrogels. This strategy not only provides a new idea for the synthesis of the hydrogel containing hydrophilic and hydrophobic materials but also opens an avenue to fabricate multifunctional hydrogels applied in the field of bio-sensors, biological imaging, drug delivery and tissue engineering.

Novel pH-sensitive γ-irradiated low molecular weight (MW) chitosan (CS) (pre-irradiated) and poly (vinyl alcohol) (PVA) blended injectable hydrogels, crosslinked with varying concentrations of glycerol, were fabricated for drug delivery application. The effect of low MW irradiated CS on controlled drug release was evaluated to address the problem of higher viscosity and lower solubility of high MW CS. The FTIR spectra of hydrogels depicted the presence of all the incorporated functional groups and the developed interactions (physical and chemical). The surface morphology of hydrogels assessed by scanning electron microscope exhibited porous microstructure. All hydrogels were subjected to the swelling analysis in different media (water, buffer and electrolytes). The pH sensitive hydrogel samples exhibited less swelling at acidic and neutral pH while higher swelling at basic pH. CPG-0.5 showed the highest swelling at all pH media as compared to other hydrogel samples. CPG-1.0 was selected for the release analysis of drug because of its highest swelling (114.47%) in distilled water having neutral pH. It was loaded with model drug (Montelukast Sodium) during the preparation phase and studied for drug release capability. The in-vitro controlled release evaluation of hydrogel (CPG-1.0) was performed in SGF and SIF using UV-visible spectroscopy. The results confirmed their applications in injectable drug release systems as all the loaded drug was released in 30 min in SGF (pH -1.2) while the release of drug in SIF (pH -6.8) was in controlled manner (99.62% in 3 h). The improved antibacterial activity of these hydrogel films was owing to the fact that the γ-irradiated low MW CS has ruptured the bacterial cell and its metabolism more efficiently by inflowing in the cell., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Penetration of antibiotics into and through the cornea is a major limiting factor in the treatment of ocular infections. Several strategies are in vogue to overcome this limitation such as use of fortified drops, gels, and subconjunctival injections. Here, we present the fabrication of rapidly dissolving polymeric microneedle array to effectively deliver besifloxacin through the cornea. Microneedles were prepared using polyvinyl alcohol and polyvinyl pyrrolidone by the micromolding technique. The model fluoroquinolone antibiotic, besifloxacin, was loaded in 36 microneedles arranged in a 6 × 6 array format within a 1 cm 2 area. The average height and base width of microneedles was 961 ± 27 and 366 ± 16 μm, respectively. Each microneedle array contained 103.4 ± 8.5 μg of besifloxacin. Cryosectioning and confocal microscopy of excised human cornea revealed that microneedles penetrated to a depth of up to 200 μm. Microneedles were found to completely dissolve in the cornea within 5 min. Application of microneedles for 5 min significantly (p < 0.05) improved the besifloxacin deposition and permeation through the cornea compared with free besifloxacin solution. Similarly, besifloxacin-loaded microneedles showed greater antibacterial activity in Staphylococcus aureus-infected cornea in comparison to free besifloxacin solution. Taken together, rapidly dissolving microneedles can be developed to effectively deliver besifloxacin to treat bacterial infections in the cornea and eye.

Purpose: To address the feasibility of infusion of yttrium-90 ( 90 Y) glass microspheres directly through the right inferior phrenic artery (RIPA)., Materials and Methods: From November 2015 to May 2017, 20 patients underwent 90 Y radioembolization through the RIPA. When the systemic-to-pulmonary shunt was demonstrated on C-arm computed tomography (CT) of the RIPA, prophylactic embolization by polyvinyl alcohol (PVA) particles was performed prior to infusion of 90 Y glass microspheres. Follow-up CT scans were retrospectively reviewed for pulmonary complications. Tumor response was determined by the modified Response Evaluation Criteria in Solid Tumors., Results: Nine (45%) patients had systemic-to-pulmonary shunts on C-arm CT images of the RIPA. The feeder of the systemic-to-pulmonary shunt was the azygoesophageal branch (n = 7) and the anterior branch (n = 2). The mean activity of 90 Y glass microspheres infused into the RIPA was 0.49 GBq (range, 0.19-1.55 GBq). No patient had symptomatic radiation pneumonitis or cutaneous complications during follow-up. Seven patients had focal atelectasis (n = 5), focal ground-glass opacity (n = 2), and/or a small amount of pleural effusion (n = 2) on follow-up image. Best tumor response fed by the RIPA was complete response (n = 4), partial response (n = 9), stable disease (n = 2), progressive disease (n = 4), and unevaluable (n = 1)., Conclusion: The administration of 90 Y glass microspheres through the RIPA may be safe after embolization of a systemic-to-pulmonary shunt identified on C-arm CT., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

The features rendering orodispersible films (ODFs) patient-centric formulations are widely discussed in the scientific literature. However there is a lack of research studies exploring ODF characteristics with a potential impact on end-user acceptability. The aim of this study was to identify the key ODF characteristics affecting end-user acceptability by developing in vitro test methods for the prediction of ODFs acceptability and correlate these formulation characteristics with the data obtained from a human panel study. Four drug-free single-polymer films were prepared by solvent casting. Solutions of poly(vinyl) alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395 KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop methods were used to assess disintegration time. A human panel of 24 healthy young adults was employed to identify end-user acceptability criteria of the four study film samples. Texture analysis data of ODF tack were not found to be in agreement with the in vivo perceived stickiness in the mouth. However, measurement of the area under the adhesive force curve obtained by DMA correlated with in vivo perceived stickiness data for all samples. The disintegration times obtained by drop method were more comparable to human panel data than the petri dish method. Hence DMA and drop methods proved to be promising methodologies for the prediction of the end-user acceptability. The type and molecular weight of the film-forming polymer had a strong influence on stickiness perception, whereas only polymeric molecular weight influenced perceived disintegration time. The human panel study showed that Participant Reported Outcomes (PROs) for the perceived stickiness in the mouth and disintegration time of test films received significantly different scores between samples, and thus were identified as the key attributes with the potential to affect the end-user acceptability. ODF stickiness and disintegration time should therefore be evaluated at an early stage of the drug product design., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, we investigated the viscoelastic and mechanical behaviour of polyvinyl alcohol films formulated along with carrageenan, plasticizing agents (polyethylene glycol and glycerol), and when loaded with nanoparticles as a model for potential applications as microbicides. The storage modulus, loss modulus and glass transition temperature were determined using a dynamic mechanical analyzer. Films fabricated from 2% to 5% polyvinyl alcohol containing 3 mg or 5 mg of fluorescently labeled nanoparticles were evaluated. The storage modulus and loss modulus values of blank films were shown to be higher than the nanoparticle-loaded films. Glass transition temperature determined using the storage modulus, and loss modulus was between 40-50℃ and 35-40℃, respectively. The tensile properties evaluated showed that 2% polyvinyl alcohol films were more elastic but less resistant to breaking compared to 5% polyvinyl alcohol films (2% films break around 1 N load and 5% films break around 7 N load). To our knowledge, this is the first study to evaluate the influence of nanoparticle and film composition on the physico-mechanical properties of polymeric films for vaginal drug delivery.

Nasal packs are widely used after septoplasty and turbinectomy. We conducted a prospective, randomized, controlled clinical trial including 100 patients who underwent septoplasty with/or without turbinectomy randomized into two groups. In the first group (the Merocel group), a standard tampon was inserted at the end of surgery. In the second group (the glove finger group), the tampon was first placed inside a glove finger. The main outcomes measured were pain and bleeding during the postoperative period and during tampon removal. Consumption of pain killers and tranexamic acid were also recorded. The mean visual analog scale score 12 hours after surgery and during tampon removal in the Merocel group were 6.78 and 8.92, respectively, compared to 4.06 and 5.27, respectively, in the glove finger group (p < 0.001). A statistically significant difference in the bleeding rate and tranexamic acid consumption during tampon removal in favor of the Merocel group was shown (p < 0.001). The use of Merocel in a glove finger is significantly less painful, although a higher chance of bleeding is reported. The influence of the surgeon's experience in using this technique needs further investigation.

Due to changing lifestyles of modern world, cardiac failures are increasing day by day. Drug delivery systems that can overcome the drawbacks of conventional drug administration are highly desired. Diltiazem hydrochloride (DTZ) is a common and effective drug used for cardiac failures. However, its efficient loading, high bio availability and sustained transdermal release from polymer matrix are of high demand. Herein, the main objective was to fabricate a transdermal drug delivery system (TDDS) capable of efficient DTZ loading with sustained release. Owing to the high hydrophilicity of DTZ, a hydrophilic matrix comprising of poly ethylene glycol coated vinyl trimethoxy silane-g-chitosan (PEG@VTMS-g-CS) was developed. DTZ encapsulated copolymer was dispersed in matrices like sodium alginate (ALG), carboxy methyl cellulose (CMC) and poly vinyl alcohol (PVA). Economic viability and cosmetic attractiveness of the films were evaluated and optimum results were obtained for PVA matrix. The in vitro skin penetration study of DTZ on rat skin further demonstrated the efficacy of PVA based film which yielded more than 40.0% cell viability on HaCaT and PBMC cell line with no histological changes on the skin which further confirmed the practical utility of the prepared film., (Copyright © 2017 Elsevier B.V. All rights reserved.)