Advances in Poly(4-aminodiphenylaniline) Nanofibers Preparation by Electrospinning Technique.

Polyaniline (PANI) nanofibers are drawing a great deal of interest from academia and industry due to their multiple applications, especially in biomedical field. PANI nanofibers were successfully electrospun for the first time by MacDiarmid and co-workers at the beginning of the millennium and since then many efforts have been addressed to improve their quality. However, traditional PANI prepared from aniline monomer shows some drawbacks, such as presence of toxic (i.e., benzidine) and inorganic (salts and metals) co-products, that complicate polymer post-treatment, and low solubility in common organic solvents, making hard its processing by electrospinning technique. Some industrial sectors, such as medical and biomedical, need to employ materials free from toxic and polluting species. In this regard, the oxidative polymerization of N-(4-aminophenyl)aniline, aniline dimer, to produce poly(4-aminodiphenylaniline), P4ADA, a kind of PANI, represents an innovative alternative to the traditional synthesis because the obtained polymer results free from carcinogenic and/or polluting co-products, and, moreover, more soluble than traditional PANI. This latter feature can be exploited to obtain P4ADA nanofibers by electrospinning technique. In this paper we report the advances obtained in the P4ADA nanofibers electrospinnig. A comparison among polyethylene oxide (PEO), polymethyl methacrylate (PMMA) and polystyrene (PS), as the second polymer to facilitate the electrospinning process, is shown. In order to increase the conductivity of P4ADA nanofibers, two strategies were adopted and compared: selective insulating binder removal from electrospun nanofibers by a rinsing tratment, afterwards optimizing the minimum amount of binder necessary for the electrospinning process. Moreover, the effect of PEO/P4ADA weight ratio on the fibers morphology and conductivity was highlighted.

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.

Electrospinning of polyaniline: effect of different raw sources.

Nanofibers of conducting polymers, as polyaniline (PANI), have received a great deal of attention by the scientific community for their potential applications (electronic, magnetic, biomedical, optical fields). Recently the electrospinning has emerged as a promising technique to produce wires and fibers of polymers with diameters ranging from 10 nm to 10 microm. PANI shows poor processability by electrospinning due to its low solubility in common solvents. However, it is possible to spin polyaniline nanofibers adding another polymer to the organic solutions, generally an insulator, necessary to increase the viscosity of the polymeric solution to be spun. Unfortunately, the presence of an insulator copolymer decreases the fibers conductivity. The key factor to obtain fibers of good quality (high conductivity and a narrow distribution of the diameters) is to reduce the amount of insulator copolymer in the spun process. Accordingly, we prepared raw PANI following different synthetic methods to be compared, aiming at the best optimized protocol in terms of easy solubility and enhanced spinning behavior of the polymers achieved. All the materials have been characterized by FT-IR and UV-VIS spectroscopies. The spun samples obtained have been characterized by SEM to evaluate the fiber morphology and complex impedance spectroscopy (EIS) in order to measure the electrical conductivity.

Percutaneous image-guided radiofrequency ablation in the therapeutic management of hepatocellular carcinoma.

Owing to surveillance programs for detection of hepatocellular carcinoma (HCC) in patients with cirrhosis, more tumors are being detected at an early, asymptomatic stage. Percutaneous ablation is considered the best treatment option for patients with Child-Pugh class A or B cirrhosis and a single, nodular-type HCC smaller than 5 cm or as many as three HCC lesions, each smaller than 3 cm, when surgical resection or liver transplantation is not suitable. Radiofrequency ablation (RFA) has emerged as the most powerful method for percutaneous treatment of early-stage HCC. Recent studies have shown that RFA can achieve more effective local tumor control than ethanol injection and with fewer treatment sessions. In a randomized trial, local recurrence-free survival rates were significantly higher in patients who received RFA than in those treated by ethanol injection, and treatment allocation was confirmed as an independent prognostic factor by multivariate analysis. Due to advances in radiofrequency technology, RFA also has been used to treat patients with more advanced tumors. Preliminary reports have shown that RFA performed after balloon catheter occlusion of the hepatic artery, transarterial embolization, or chemoembolization results in increased volumes of coagulation necrosis, thus enabling successful destruction of large HCC lesions. This report reviews the current status of percutaneous, image-guided RFA in the therapeutic management of HCC.