A Review on Membranes for Clinical Treatment and Drug Delivery in Medical Applications

Membrane processes are used extensively in biomedical applications. This state of the art review presents the main applications including renal kidney, blood filtration, blood oxygenator, artificial liver, artificial pancreas, and drug delivery devices. For well-established treatments like dialysis, plasmapheresis, and blood oxygenator, the techniques are summarized by presenting membranes used, devices, configurations and treatments. The artificial liver and the artificial pancreas are not clinically used and some main aspects related to the development of these devices are given, including configurations and liver or pancreatic cells. Finally, drug delivery devices based on membranes, which are an important area in pharmaceutics, are summarized by focusing on diffusion and transdermal delivery systems, as well as colloids like liposomes and nanocapsules. These colloids with nanometric size are surrounded by a lipidic or polymeric thin membrane which controls drug transfer to the surrounding medium

Comparison of Three Processes for Parenteral Nanoemulsion Production: Ultrasounds, Microfluidizer, and Premix Membrane Emulsification

International audienceNanoemulsions are of great interest for pharmaceutical applications, including parenteral dosage forms. However, their production is still limited and requires more efficient and adaptive technologies. The more common systems are high-shear homogenization like microfludizers (MF) at industrial scale and ultrasounds at research scale, both based on high energy limiting their application for sensitive drugs. Recently, a process based on premix membrane emulsification (PME) was developed to produce nanoemulsions. These three processes have been compared for the production of a model parenteral nanoemulsion containing all-trans-retinoic acid, a thermolabile molecule which is used in the treatment of acute promyelocytic leukemia in a parenteral form. Droplet size and active integrity were studied because of their major interest for efficacy and safety assessment. Regarding droplet size, PME produced monodispersed droplets of 335 nm compared to the other processes which produced nanoemulsions of around 150 nm but with the presence of micron size droplets detected by laser diffraction and optical microscopy. No real difference between the three processes was observed on active degradation during emulsifcation. However, regarding stability, especially at 40 o C nanoemulsions obtained with the microfluidizer showed a greater molecule degradation and unstable nanoemulsion with a 4 times droplet size increase under stress conditions

Removal of Diclofenac from Water using an Hybrid Process Combining Activated Carbon Adsorption and Ultrafiltration or Microfiltration

Small amounts of pharmaceuticals are increasingly found in natural waters and wastewaters in treatment plants. Several processes are developed for their removal such as hybrid membrane processes. These techniques integrate membrane filtration (mainly ultrafiltration or microfiltration) to a physical technique (such as flocculation or sorption on activated carbon). In this study, we report results on a process with sorption on activated carbon and microfiltration or ultrafiltration using a ceramic membrane, with a specific attention to the influence of the membrane pore size. The membranes showed little fouling at the experimental conditions used (maximum 500 mg/L activated carbon), while an important increase in conductivity was observed in permeate samples due to the salting out of ions from the activated carbon particles. Besides, the removal of diclofenac and humic acid (both at 10 mg/L) was higher than 90 % during the treatment with both ultrafiltration and microfiltration, however microfiltration was preferred due to its higher flux. These results suggest that hybrid processes of activated carbon/ultrafiltration or microfiltration could be interesting alternatives for processing waters containing small amounts of pharmaceuticals

Sorption de biomolécules par membrane échangeuse d’ions : étude expérimentale et modélisation

AbstractMicroporous membranes are an alternative to conventional packed columns chromatography. They offer the main advantage compared to bulk material to reduce diffusion phenomena, reduce residence time and pressures drops, and thus, facilitate rapid purification of large quantities of molecules. A wide range of chromatographic membranes involving different molecules retention mechanism (ion exchange, affinity, etc…) is now commercialized. Despite their success, the influence of the geometry of the membrane chromatography devices remains relatively unexplored from a theoretical point of view.This study on the sorption of bovine serum albumin (BSA) on a chromatographic ion exchange membrane (type Sartobind Q from Sartorius Stedim Biotech-Goettingen, Germany), aims to experimentally evaluate the influence of operating conditions (fluid flowrate, initial concentrations) on the breakthrough curves. Two types of geometries (plane module or spiral module) were used and helped to highlight the influence of the type of flow (axial or radial) on separation. The experimental study was conducted on an Akta Prime chromatography system (General Electrics, France). In order to understand the observed phenomena, to predict the performance of different modules and to develop a tool for improving the design of membrane chromatography capsule, a mathematical model was developed in CFD (Computational Fluid Dynamics) and successfully simulated

Preparation of liposomes: a novel application of microengineered membranes-from laboratory scale to large scale

A novel ethanol injection method using microengineered nickel membrane was employed to produce POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and Lipoid® E80 liposomes at different production scales. A stirred cell device was used to produce 73 ml of the liposomal suspension and the product volume was then increased by a factor of 8 at the same transmembrane flux (140 l m−2 h−1), volume ratio of the aqueous to organic phase (4.5) and peak shear stress on the membrane surface (2.7 Pa). Two different strategies for shear control on the membrane surface have been used in the scaled-up versions of the process: a cross flow recirculation of the aqueous phase across the membrane surface and low frequency oscillation of the membrane surface (∼40 Hz) in a direction normal to the flow of the injected organic phase. Using the same membrane with a pore size of 5 μm and pore spacing of 200 μm in all devices, the size of the POPC liposomes produced in all three membrane systems was highly consistent (80–86 nm) and the coefficient of variation ranged between 26 and 36%. The smallest and most uniform liposomal nanoparticles were produced in a novel oscillating membrane system. The mean vesicle size increased with increasing the pore size of the membrane and the injection time. An increase in the vesicle size over time was caused by deposition of newly formed phospholipid fragments onto the surface of the vesicles already formed in the suspension and this increase was most pronounced for the cross flow system, due to long recirculation time. The final vesicle size in all membrane systems was suitable for their use as drug carriers in pharmaceutical formulations

Vitamin E encapsulation within pharmaceutical drug-carriers prepared using membrane contactors

Vitamin E encapsulation within pharmaceutical drug-carriers prepared using membrane contactor

Preparation of liposomes: a novel application of microengineered membranes

Liposomes with a mean size of 59–308 nm suitable for pulmonary drug delivery were prepared by the ethanol injection method using nickel microengineered flat disc membranes with a uniform pore size of 5–40 μm and a pore spacing of 80 or 200 μm. An ethanolic phase containing 20–50 mg ml−1 phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or Lipoid® E80), 5–12.5 mg ml−1 stabilizer (cholesterol, stearic acid or cocoa butter), and 0 or 5 mg ml−1 vitamin E was injected through the membrane into an agitated aqueous phase at a controlled flux of 142–355 l m−2 h−1 and a shear stress on the membrane surface of 0.80–16 Pa. The mean particle size obtained under optimal conditions was 84 and 59 nm for Lipoid E80 and POPC liposomes, respectively. The particle size of the prepared liposomes increased with an increase in the pore size of the membrane and decreased with an increase in the pore spacing. Lipoid E80 liposomes stabilized by cholesterol or stearic acid maintained their initial size within 3 months. A high entrapment efficiency of 99.87% was achieved when Lipoid E80 liposomes were loaded with vitamin E. Transmission electron microscopy images revealed spherical multi-lamellar structure of vesicles. The reproducibility of the developed fabrication method was high

Production of liposomes using microengineered membrane and co-flow microfluidic device

Two modified ethanol injection methods have been used to produce Lipoid® E80 and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) liposomes: (i) injection of the organic phase through a microengineered nickel membrane kept under controlled shear conditions and (ii) injection of the organic phase through a tapered-end glass capillary into co-flowing aqueous stream using coaxial assemblies of glass capillaries. The organic phase was composed of 20 mg ml−1 of phospholipids and 5 mg ml−1 of cholesterol dissolved in ethanol and the aqueous phase was ultra-pure water. Self-assembly of phospholipid molecules into multiple concentric bilayers via phospolipid bilayered fragments was initiated by interpenetration of the two miscible solvents. The mean vesicle size in the membrane method was 80 ± 3 nm and consistent across all of the devices (stirred cell, cross-flow module and oscillating membrane system), indicating that local or temporal variations of the shear stress on the membrane surface had no effect on the vesicle size, on the condition that a maximum shear stress was kept constant. The mean vesicle size in co-flow microfludic device decreased from 131 to 73 nm when the orifice diameter in the injection capillary was reduced from 209 to 42 μm at the aqueous and organic phase flow rate of 25 and 5.55 ml h−1, respectively. The vesicle size was significantly affected by the mixing efficiency, which was controlled by the orifice size and liquid flow rates. The smallest vesicle size was obtained under conditions that promote the highest mixing rate. Computational Fluid Dynamics (CFD) simulations were performed to study the mixing process in the vicinity of the orifice

pH-sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method

A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, Mn (9200 or 10 400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m–2 h–1 of the organic phase (a 1 mg mL–1 solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of 75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of −19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions

Preparation of nanomaterials for food applications using membrane emulsification and membrane mixing

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