Evaluation of surface properties of erythrocyte membranes in liver diseases

Background: The physicochemical properties of Red Blood Cell membranes (RBC) are altered in liver diseases. Langmuir monolayers offer an excellent model system to study biological membrane surface properties. The aim of this study was to evaluate surface properties of erythrocyte membranes in liver diseases.  Methods: Sixty-one patients with various liver diseases and fifteen controls were enrolled. Surface properties of RBC membrane were evaluated using Langmuir monolayers. Surface pressure area isotherms were recorded at body temperature using RBC membrane lipid extract. Student’s t-test and Analysis of variance tests were performed.Results: Mean maximum surface pressure and hysteresis area were significantly higher in cirrhotic and non-cirrhotic liver disease groups compared to controls. Within cirrhotics, mean maximum surface pressure and lift off area was significantly lower in the Child C group as compared to the Child A, B and A-B groups. The mean hysteresis area was significantly lower in the Child C group as compared to the Child B and A-B groups.Conclusion: The results of our study confirmed high rigidity of RBC membrane in mild and moderate liver cirrhosis and high fluidity in severe liver cirrhosis. This study may pave the way to the development of a surface activity based biophysical tool for therapeutic implication in liver diseases.

Advances in intravesical drug delivery systems to treat bladder cancer

Chemotherapeutic agents administered intravesically to treat bladder cancer have limited efficacy due to periodic dilution and wash-out during urine formation and elimination. This review describes the pathophysiology, prevalence and staging of bladder cancer, and discusses several formulation strategies used to improve drug residence within the bladder. These include the use of amphiphilic copolymers, mucoadhesive formulations, hydrogels, floating systems, and liposomes. Various in vitro and in vivo models recently employed for intravesical drug delivery studies are discussed. Some of the challenges that have prevented the clinical use of some promising formulations are identified

Innovative Methods and Applications in Mucoadhesion Research.

The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2-3 September 2015 as a satellite event of the ICCC 13th-EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented. Then a selection of preparative techniques and testing methods are described (at molecular as well as micro and macroscale) that may support the pharmaceutical development of mucus interactive systems and assist formulators in the scale-up and industrialization steps. Recent applications of mucoadhesive systems (including medical devices) intended for different routes of administration (oral, gastrointestinal, vaginal, nasal, ocular, and intravesical) and for the treatment of difficult to treat pathologies or the alleviation of symptoms are described

Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot

The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel. This allows enhanced drug permeation while maintaining a localization of the drug depot. LG-PTX had an IC50 of 325 +/- 117 nM in B16F10 melanoma cells, and cytotoxicity with concurrent doses of fractionated radiation showed significant increase in apoptotic cells (75%) compared to radiation (39%) or LG-PTX (43%) alone. Peri-tumoral injection in tumor-bearing mice showed PTX localization in the tumor 2 hours after administration, with no drug detected in plasma or other organs. LG-PTX administration with doses of focal radiation (5x3 Gy) significantly reduced tumor volumes compared to control (6.4 times) and radiation alone (1.6 times) and improved animal survival. LG-PTX thus efficiently localizes the drug at the tumor site and synergistically enhances the effect of concurrent radiotherapy. This novel liposome-in-gel system can potentially be used as a platform technology for the delivery of radiosensitizing drugs to enhance the efficacy of chemoradiotherapy