Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

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 AUC0-96 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.

Transcatheter Arterial Sclerosing Embolization for the Treatment of Giant Propranolol-Resistant Infantile Hemangiomas in the Parotid Region.

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.

Lappaconitine trifluoroacetate contained polyvinyl alcohol nanofibrous membranes: Characterization, biological activities and transdermal application.

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 (LD50 of 21.14 mg·kg-1), improved analgesic effect and longer half-life (T1/2 of 2.24 h) when compared with LAH. Moreover, in vitro transdermal permeation (Jss 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.

Future liver remnant growth after various portal vein embolization regimens: a quantitative comparison.

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.

New bioresorbable wraps based on oxidized polyvinyl alcohol and leukocyte-fibrin-platelet membrane to support peripheral nerve neurorrhaphy: preclinical comparison versus NeuraWrap.

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.

Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases.

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 × 105 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.

Electrospun Membranes Based on Schizophyllan-PVOH and Hamamelis Virginiana Extract: Antimicrobial Activity Against Microorganisms of Medical Importance.

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.

γ-Irradiated chitosan based injectable hydrogels for controlled release of drug (Montelukast sodium).

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.

Polyvinyl alcohol terminal chemoembolization for hepatocellular carcinoma with hepatic arteriovenous shunts: Safety, efficacy, and prognostic factors.

PURPOSE: To evaluate the safety and efficacy of polyvinyl alcohol (PVA) terminal chemoembolization and to identify the prognostic factors associated with survival in hepatocellular carcinoma (HCC) patients with hepatic arteriovenous shunts (HAVS). MATERIALS AND METHODS: Of 133 patients' managements were retrospectively analyzed. HAVS was classified into three types: slow-flow, intermediate-flow and high-flow. The size of the PVA used was determined following the scheme: slow-flow HAVS: 300-500µm PVA; intermediate-flow HAVS: 500-710µm PVA; high-flow HAVS: 710-1000µm PVA. The HCCs with slow-flow and intermediate-flow HAVS were embolized by PVA plus chemotherapeutic agents lipiodol emulsion, while the high-flow HAVS were treated by PVA with chemotherapeutic agents. Survival curves were calculated by Kaplan-Meier method and compared by log-rank test. The influence of possible prognostic factors on survival were analyzed by multivariate Cox proportional-hazards method. RESULTS: The median overall survival (OS) of 133 patients was 9.1 months. The median OS of the slow-flow type, intermediate-flow type and high-flow type patients were 10.8, 9.1 and 7.3 months, respectively. There was no statistically significant difference among different HAVS types (P=0.239). The 30-day mortality was 3.8%. Cox multivariate survival analysis revealed that initial preoperative AFP value≥400ng/ml (HR=2.105, P=0.006) was an independent risk factor. While multiple embolization (HR=0.482, P=0.011), tumor remission (HR=0.431, P=0.041) and multimodality therapy (HR=0.416, P=0.004) were independent protection factors. CONCLUSION: It is safe and effective for HCCs with HAVS treated by terminal chemoembolization therapy with PVA plus chemotherapeutic agents lipiodol emulsion (or PVA plus chemotherapeutic agents). The HCCs with HAVS achieves good prognosis with multiple embolization, tumor remission and multimodality therapy, while achieves poor prognosis with inital preoperative high AFP value (≥400ng/ml).

Transarterial embolization/chemoembolization therapy for hepatocellular carcinoma fed by adrenal artery: Preliminary results.

To assess the value of transarterial embolization/chemoembolization (TAE/TACE) therapy via adrenal artery for patients with hepatocellular carcinoma (HCC). Patients with HCC who underwent TAE/TACE therapy via adrenal artery between May 2003 and October 2015 across 4 medical centers were identified. Clinical information, procedural data, and imaging data were analyzed to assess technical success, disease control, and survival rates. A t test was used to compare the differences in serum alpha-fetoprotein before and after treatment. A total of 23 patients (23 men; mean age, 54.6 ±â€Š7.5 years; range, 37-72 years) were included in this study. All tumors were located under the capsule of the liver and adjacent to the adrenal gland (median tumor diameter, 8.2 cm). Lesions fed by the adrenal artery were demonstrated during initial TAE/TACE in 7 patients and during repeat TAE/TACE in 16 patients. The superior, middle, and inferior adrenal arteries were involved in 14, 3, and 6 patients, respectively. The technical success rate was 100%. The disease control rate at 3 months was 100%, with partial tumor response seen in 16 (69.6%) patients and stable disease seen in 7 (30.4%) patients. The cumulative survival rate from the time of TAE/TACE was 100% at 1 year. There were no embolization-related complications. TAE/TACE therapy via the adrenal arteries can improve the therapeutic efficacy of TAE/TACE and reduce the incidence of HCC recurrence and/or presence of residual HCC.

Technically Successful Geniculate Artery Embolization Does Not Equate Clinical Success for Treatment of Recurrent Knee Hemarthrosis after Knee Surgery.

PURPOSE: To evaluate technical details, clinical outcomes, and complications in patients undergoing geniculate artery embolization for treatment of spontaneous hemarthrosis after knee surgery. MATERIALS AND METHODS: During 2009-2014, 10 consecutive patients (seven women; mean age, 57.4 y) underwent geniculate artery embolization at a single tertiary care center. All patients except one had hemarthrosis after total knee replacement (TKR). One patient presented with hemarthrosis after cartilage surgery. Two patients in the TKR group had a history of TKR revisions before the embolization. Embolization was performed with polyvinyl alcohol particles (range, 300-700 µm). In one patient requiring repeat embolization, N-butyl cyanoacrylate/ethiodized oil was used. The endpoint for embolization was stasis in the target artery and elimination of the hyperemic blush. RESULTS: In 10 patients, 14 embolizations were performed with 100% technical success. Hemarthrosis resolved in six patients. Four patients required repeat embolization for recurrent hemarthrosis, which subsequently resolved in two of four patients. Three of the four patients who required repeat embolization had serious comorbidities, either blood dyscrasias or therapeutic anticoagulation. There were two minor skin complications that resolved with conservative management. The average length of follow-up after embolization was 545 days (range, 50-1,655 d). One patient was lost to follow-up. CONCLUSIONS: Geniculate artery embolization is a safe, minimally invasive treatment option for spontaneous and refractory knee hemarthrosis after knee surgery with 100% technical success. However, limited clinical success and higher repeat embolization rates were noted in patients with serious comorbidities.

Marked effects of combined TPGS and PVA emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles: in vitro and in vivo evaluation.

The purpose of this study was to investigate the effect of d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) alone or in combination with other emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles for in vivo applications. Nanoparticles were prepared by nanoprecipitation or single-emulsion solvent evaporation method using TPGS alone or in combination with other surfactants. These nanoparticles were fully characterized by different techniques. For nanoprecipitation preparations, by adding 0.1% TPGS to polyvinyl alcohol in the aqueous phase, encapsulation efficiency markedly increased (up to 82%); moreover, drug release was readily controlled up to 3 days. Regarding emulsion solvent evaporation method, the highest encapsulation efficiency was obtained for nanoparticles emulsified with polyvinyl alcohol or TPGS; however, the burst release was high. When the combination of TPGS and polyvinyl alcohol was applied a marked increase in encapsulation efficiency (∼ 90%) was observed and the drug release was extended to more than one week. Pharmacokinetic measurements showed that the optimum formulation generated 14.4 times higher AUC and lasted 5.1 times longer when compared to free drug. Overall, using TPGS in combination with polyvinyl alcohol as an emulsifier in preparing etoposide loaded PLGA-PEG nanoparticles markedly increased the encapsulation efficiency, sustained drug release and resulted in nanoparticles with noticeable sustainable in vivo disposition.

Primary in vitro and in vivo evaluation of norcantharidin-chitosan/poly (vinyl alcohol) for cancer treatment.

Two novel polymer-drug conjugates norcantharidin-poly(vinyl alcohol) and norcantharidin-chitosan (NCTD-PVA and NCTD-CS) were synthesized via alcoholysis reaction and characterized by (1)H-NMR and FTIR. NCTD was released from the conjugates via hydrolysis, faster in PBS (pH 5.0) than that in PBS (pH 7.4). NCTD-PVA and NCTD-CS inhibited human esophageal carcinoma ECA-109 cell and murine breast cancer EMT6 cell growth in a dose-dependent manner. The IC50 values of NCTD, NCTD-PVA and NCTD-CS on ECA-109 cell at 48 h were 9.4 ± 0.9, 55.3 ± 3.0 and 168.8 ± 8.9 µg/ml, respectively, and the IC50 values of the three compounds on EMT6 cell were 3.1 ± 0.3, 30.5 ± 5.4 and 90.7 ± 8.1 µg/ml, respectively. The two conjugates both induced esophageal carcinoma ECA-109 cell apoptosis and arrested cell cycle at the S phase. Caspase-8 and caspase-3 were activated in the ECA-109 cell after incubating with NCTD-PVA or NCTD-CS. The primary in vivo antitumor activity was assessed in the EMT6 tumor-bearing mouse model. NCTD-PVA and NCTD-CS displayed higher tumor inhibition rates than that of free NCTD.

Research of novel biocompatible radiopaque microcapsules for arterial embolization.

Embolic agents, such as microparticles, microspheres or beads used in current embolotherapy are mostly radiolucent, which means the agents are invisible under X-ray imaging during and after the process of embolization, and the fate of these particles cannot be precisely assessed. In this research, a radiopaque embolic agent was developed by encapsulating lipiodol in polyvinyl alcohol. The lipiodol-containing polyvinyl alcohol microcapsules (LPMs) were characterized and evaluated for their morphology, size distribution, lipiodol content, lipiodol release, elasticity, and deliverability through catheter. The radiopacity of LPMs in vials and in living mice was both detected by an X-ray imaging system. The biocompatibility of LPMs was investigated with L929 cells and in mice after subcutaneous injection. Embolization of LPMs to a rabbit kidney was performed under digital subtraction angiography (DSA) and the radiopacity of LPMs was verified by computed tomography (CT).

Sprague-Dawley rats bearing McA-RH7777 cells for study of hepatoma and transarterial chemoembolization.

AIM: To evaluate the feasibility of the McA-RH7777 tumor model in Sprague-Dawley (SD) rats, for study of hepatoma and transarterial chemoembolization. MATERIALS AND METHODS: McA-RH7777 rat hepatoma cells (1×10(7)) were inoculated into the left hepatic lobe of SD rats (n=38). Chemoembolization with left common carotid artery access was performed using an emulsion of iodized oil and doxorubicin, and polyvinyl alcohol particles. Tumor induction rate and response to chemoembolization were assessed by magnetic resonance imaging and histology. RESULTS: Tumor induction rate of McA-RH7777 in SD rat livers was 73.3% (11/15). Hematoxylin-and-eosin staining revealed hypercellular tumor with a trabecular pattern that mimics human hepatocellular carcinoma. Chemoembolization was successfully conducted in all rats. There was a significant difference in tumor growth rates between the chemoembolization-treated and control groups (p<0.0001). CONCLUSION: A rat tumor model of McA-RH7777 cells in SD rats is feasible and has the potential to be a good model for hepatoma and chemoembolization studies.

Pharmacokinetic evaluation of intranasally administered vinyl polymer-coated lorazepam microparticles in rabbits.

The intranasal (IN) administration of lorazepam is desirable in order to maximize speed of onset and minimise carry-over sedation; however, this benzodiazepine is prone to chemical hydrolysis and poor airway retention, and thus, innovative epithelial presentation is required. The aim of this study was to understand how the in situ self-assembly of a mucoretentive delivery system, formed by the dissolution of vinyl polymer-coated microparticles in the nasal mucosa, would influence lorazepam pharmacokinetics (PK). IN administration of the uncoated lorazepam powder (particle size, 6.7 ± 0.1 µm) generated a biphasic PK profile, which was indicative of sequential intranasal and oral absorption (n = 6; dose, 5 mg/kg). Coating the drug with the vinyl polymer, MP1 (9.9 ± 0.5 µm with 38.8 ± 14.0%, w/w lorazepam) and MP2 (10.7 ± 0.1 µm with 47.0 ± 1.0%, w/w lorazepam), allowed rapid systemic absorption (MP1, T (max) 14.2 ± 4.9 min; MP2, T (max) 9.3 ± 3.8 min) in rabbits and modified the PK profiles in a manner that suggested successful nasal retention. The poly(vinyl pyrrolidone)-rich MP2 system provided the best comparative bioavailability, it prolonged the early-phase nasal drug absorption and minimised drug mucociliary clearance, which correlated well with the intermolecular hydrogen-bond-driven vinyl polymer interactions observed in vitro.

Hepatocellular necrosis, apoptosis, and proliferation after transcatheter arterial embolization or chemoembolization in a standardized rabbit model.

PURPOSE: To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model. MATERIALS AND METHODS: Rabbits implanted with VX2 tumors in left liver lobes were randomly divided into three groups: a control group (n = 9) that underwent infusion of distilled water into the left hepatic artery, an embolization group (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol (PVA) particles, and a chemoembolization group (n = 15) that underwent left hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil followed by PVA embolization. Serum and liver samples were collected at 6 hours, 3 days, and 7 days postoperatively. Liver damage was measured by liver function tests and histologic analysis. Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling were performed to quantify proliferating and apoptotic cells. Serum tumor necrosis factor (TNF)-α levels were measured to assess proinflammatory response. RESULTS: Compared with embolization, chemoembolization caused liver injury with a greater increase in serum alanine aminotransferase and aspartate aminotransferase levels on days 3 and 7; histologic analysis showed increased hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum levels of TNF-α at 6 hours. By contrast, chemoembolization resulted in a slower increase in hepatocyte proliferation. Additionally, increased apoptotic hepatocytes were observed after embolization and chemoembolization. CONCLUSIONS: In contrast to embolization, nonsuperselective transcatheter arterial chemoembolization increased hepatocellular damage and stimulated systemic proinflammatory cytokine release, but inhibited hepatocyte proliferation.

Preliminary clinical assessment of polyvinyl alcohol-tetrahydroxyborate hydrogels as potential topical formulations for local anesthesia of lacerations.

OBJECTIVES: The aim of this study was to assess a novel semisolid material as a potential topical drug delivery system for acute laceration. The objectives were to correlate physical characterization data using rheologic studies and to compare with clinical assessment of performance in an emergency department (ED). METHODS: Polyvinyl alcohol (PVA) hydrogels, cross-linked using tetrahydroxyborate (THB), were characterized using texture profile analysis. Formulation samples were applied to acute lacerations presented to the ED and factors, such as in vivo residency time and cohesive removal, were assessed. RESULTS: Viscosity was shown to be related to mechanical characteristics, whereas adhesiveness depended on the THB concentration. Residence in, and clean removal from, lacerations was evaluated on 29 patients. Formulation F3 (10.0% PVA, 2.5% w/w THB) displayed the most appropriate characteristics for clinical use by scoring highest in qualitative assessments. Other formulations exhibited difficulties in application and removal due to excessive adhesiveness. The release of a model local anesthetic drug was proportional to the concentration of drug incorporated, but was not substantially affected by small changes in the formulation constituents. CONCLUSIONS: Using a combination of pharmaceutical evaluation and clinical assessment, it was shown that cross-linked PVA semisolids are a suitable formulation for drug administration to acute lacerations, with potential for induction of anesthesia prior to wound repair.

Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day disease-specific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n = 5) partial responses, 64% (n = 29) stable, and 24% (n = 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P = .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR + SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies.