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ABSTRACT: Drug delivery systems based on synthetic polymers are widely employed in the treatment of several pathologies. In particular, the use of implantable devices able to release one or more active principles in a topic site with a controlled delivery kinetic represents an important improvement in this field. However, the release kinetic, that could be affected by different parameters, like polymer composition or chemical nature and initial drug loading, represents one of the problems related to the implantation of delivery systems. In this study, acrylic membranes with different macromolecular composition were prepared and studied analyzing delivery kinetic properties. Drug delivery systems were prepared using as matrix the copolymer poly(methylmethacrylate-co-butylmethacrylate) in three different compositions and folic acid (less hydrophobic) or Paclitaxel (more hydrophobic) as drugs, to evaluate the effect of macromolecular composition and hydrophilicity degree on the release properties. In addition, the effect of the initial drug loading was considered, loading drug delivery systems with four different initial drug percentages. Results showed a direct dependence of kinetics from macromolecular composition, hydrophilicity degree of solutes, and initial drug loading, allowing one to conclude that it is possible to design and to develop drug delivery systems starting from poly(methylmethacrylate-co-butylmethacrylate) matrices with specific properties by varying these three parameters.
Drug Delivery 08/2010; 17(6):452-65. · 1.46 Impact Factor
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ABSTRACT: In this work, the characterization of a biodegradable bilayer system, used as controlled and combined drug delivery platform, is reported. For this aim, a bilayer system, composed of poly(lactic-co-glycolic acid) and poly(3-hydroxybutyric-co-3-hydroxyvaleric acid), was investigated under physicochemical and functional aspects by evaluating polymer/polymer and polymer/stent material interactions, the kinetic of in vitro degradation, and drug release properties, comparing results with the monolayer reference systems. Obtained results showed that the bilayer system allowed increasing the total amount of eluted Tacrolimus and Paclitaxel drugs with respect to the monolayer systems in the considered testing period and conditions. This evidence was associated to a faster degradation of the tested copolymers in the bilayered configuration, excluding a synergic effect of two drugs on delivery performance. In addition, a macromolecular relaxation process was identified to govern the PLX release from poly(lactic-co-glycolic acid), whereas a pure Fickian diffusion occurred in the delivery of Tacrolimus from poly(3-hydroxybutyric-co-3-hydroxyvaleric acid).
Journal of Biomedical Materials Research Part B Applied Biomaterials 05/2010; 93(2):375-85. · 2.15 Impact Factor
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ABSTRACT: The aim of the present work is the synthesis and characterization of polymer materials showing good adhesion, drug loading, and delivery properties, for potential cardiovascular application. In particular, poly(methylmethacrylate-co-acrylic acid) copolymers are prepared in different compositions by a radical polymerization and investigated as potential materials to coat metallic stents and to carry out a local drug release. Films obtained by dissolving the copolymer in an appropriate organic solvent (also loaded with an anti-restenosis drug, such as tacrolimus) are investigated: physicochemical properties, adhesiveness to metallic stent material, and kinetics of drug release in physiological environment are studied.
Journal of Biomaterials Applications 12/2008; 24(4):353-83. · 2.08 Impact Factor
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ABSTRACT: In this paper we concentrated on the possibility of adopting molecular imprinting technology for the preparation of polymeric membranes imprinted with phosphatidylcholine, one of the main phospholipids found in the cell membrane and lipoproteins, via phase inversion, with the intention of applying this method in the ongoing research into the regression of atherosclerosis. The polymer matrix was based on poly(ethylene-co-vinyl alcohol) with an ethylene molar content of 44% and the amount of template molecule was varied so as to obtain three different kinds of membrane. We found that they possessed elevated binding capabilities (78.6% of the initial amount of phosphatidylcholine was found to be adsorbed by the membrane) united with a very high selectivity. Similar phospholipids (phosphatidylinositol and phosphatidylethanolamine) were found to be adsorbed only in very small quantities and mostly due to the porosity of the membrane itself and not to molecular imprinting.
Biosensors & bioelectronics 08/2008; 24(4):748-55. · 5.43 Impact Factor
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ABSTRACT: A biological–synthetic hybrid material was prepared as a support for proteinic molecules. To control the conformational stability and ‘vitality’ of the entrapped compound, an enzyme, which catalyses a chemical reaction, was chosen. The physical immobilisation of α-amylase on a novel biological–synthetic hybrid material was realised using a synthetic (poly[ethylene-co-(vinyl alcohol)]) and a biological (dextran) component. The supports were obtained in the form of porous sponges using the phase inversion process. The kinetic parameters of enzymatic hydrolysis of soluble starch were obtained by determining the maltose (reaction product) concentration in the test solution by a spectrophotometric method. A high amount of enzyme (10 and 15 mg per g of polymer matrix) was successfully entrapped in the polymer support and a rather good enzyme activity of entrapped α-amylase and a constant activity for repeated use, compared with native α-amylase, were observed. The results obtained clearly indicated that the bioartificial polymer sponges, showing an immobilisation of α-amylase with maintenance of the catalytic function of the enzyme, can be used as suitable supports for proteins. Copyright © 2005 Society of Chemical Industry
Polymer International 06/2005; 54(10):1357 - 1365. · 1.90 Impact Factor
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ABSTRACT: Molecularly imprinted membranes imprinted for a large-molecular-weight protein were realised using a blend of natural and synthetic polymers. Bioartificial membranes of synthetic (poly(ethylene-co-vinyl alcohol)-EVAL, Clarene) and biological (Dextran) polymers, molecularly imprinted with alpha-amylase as the template, were prepared and investigated. Dimethyl sulfoxide (DMSO) solutions of the alpha-amylase template, Clarene and Dextran were mixed under stirring in the desired proportions and dipped in DMSO (solvent)/water (non solvent) mixture, to obtain the phase separation. The release of Clarene, Dextran and alpha-amylase in the inversion baths was quantified by spectrophotometric methods and final composition of membranes was established. To study the interactions between the polymer components and between polymeric materials and the template, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were carried out. Results indicated that stable and continuous bioartificial membranes of Clarene and Dextran can be obtained, whereby calorimetric analysis suggested the presence of high interaction between alpha-amylase and the Clarene component.
Journal of Biomaterials Science Polymer Edition 02/2005; 16(3):397-410. · 1.69 Impact Factor
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ABSTRACT: Past and recent attempts to introduce in synthetic polymers molecular information from natural substances through simple blending, template polymerization and molecular imprinting are reviewed. The most promising approaches that can open the way to the realisation of new materials with improved biocompatibility, antibody- or enzyme-like performances are analysed more deeply. The realisation of bioartificial blends from natural and synthetic polymers, molecularly imprinted nanospheres or membranes that can act as recognition element in (bio)sensing devices, as synthetic enzymes or as key constituents of body fluids purification tools is presented in order to make the reader aware of the fascinating possibilities that these techniques make available to the biomedical science and engineering in the close future. The last part of the paper describes recent attempts to insert recognition elements for large molecules as proteins, DNA segments, viruses or whole cells in synthetic polymer systems, in order to develop new systems in the treatments of diseases and for tissue-engineering applications.
Journal of Biomaterials Science Polymer Edition 02/2005; 16(2):219-36. · 1.69 Impact Factor
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ABSTRACT: Cross-linked poly(methylmethacrylate-co-methacrylic acid) nanospheres were imprinted with theophylline through template radical polymerisation in diluted acetonitrile solution. This study will focus on the effect of functional monomer nature used (methylmethacrylate and/or methacrylic acid) in the recognition and in the release of template in order to develop a material with combined properties of drug delivery and rebinding for clinical applications. After template extraction the nanospheres showed satisfactory recognition properties (up to 1mg template/g of polymer). Moreover polymers prepared selectively removed theophylline with a theophylline rebinding of 5.1 times higher than that of caffeine, a compound of similar structure. Drug release properties were also satisfactory (up to 95% of loaded theophylline in 7 days).
Biosensors and Bioelectronics 01/2005; 20(6):1083-90. · 5.60 Impact Factor
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ABSTRACT: Membranes of a synthetic (poly(ethylene-co-vinyl alcohol), Clarene) and a biological (dextran) polymer, imprinted with alpha-amylase, of different compositions were prepared by the phase-inversion process. Membrane morphologies were shown to be dependent on the synthetic-biological components composition. The removal of the template from the membranes was performed by extraction with water, while an aqueous solution of alpha-amylase was permeated across the membranes under pressure to obtain the rebinding of the template. The selectivity of alpha-amylase-imprinted membranes was investigated by the same uptake experiment using pepsin, albumin and amyloglucosidase, and the rebinding of these proteins was compared with that of the print molecule. Before and after template extraction and after the rebinding experiment, kinetic measurements of the imprinting molecule were conducted to estimate the activity of the enzyme immobilised in the polymer matrix. Results obtained revealed that the immobilised enzyme maintains a good functionality while in the membrane compared to the free enzyme and the imprinted 'bioartificial' dextran and Clarene membranes, obtained by the phase-inversion method, can establish efficient interaction with alpha-amylase as template molecule, as confirmed by the fair selectivity in rebinding tests.
Journal of Biomaterials Science Polymer Edition 02/2004; 15(3):255-78. · 1.69 Impact Factor
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ABSTRACT: Bioartificial polymeric materials, based on blends of polysaccharides with synthetic polymers such as poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA), were prepared as films or hydrogels. The physico-chemical, mechanical, and biological properties of these materials were investigated by different techniques such as differential scanning calorimetry, dynamic mechanical thermal analysis, scanning electron microscopy, and in vitro release tests, with the aim of evaluating the miscibility of the polymer blends and to establish their potential applications. The results indicate that while dextran is perfectly miscible with PAA, dextran/PVA, chitosan/PVA, starch/PVA, and gellan/PVA blends behave mainly as two-phase systems, although interactions can occur between the components. Cross-linked starch/PVA films could be employed as dialysis membranes: they showed transport properties comparable to, and in some cases better than, those of currently used commercial membranes. Hydrogels based on dextran/PVA and chitosan/PVA blends could find applications as delivery systems. They appeared able to release physiological amounts of human growth hormone, offering the possibility to modulate the release of the drug by varying the content of the biological component.
Journal of Biomaterials Science Polymer Edition 02/2001; 12(3):267-81. · 1.69 Impact Factor
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ABSTRACT: Molecular imprinting is a technique for the synthesis of polymers capable to bind target molecules selectively. The imprinting of large proteins, such as cell adhesion proteins or cell receptors, opens the way to important and innovative biomedical applications. However, such molecules can incur into important conformational changes during the preparation of the imprinted polymer impairing the specificity of the recognition cavities. The "epitope approach" can overcome this limit by adopting, as template, a short peptide sequence representative of an accessible fragment of a larger protein. The resulting imprinted polymer can recognize both the template and the whole molecule thanks to the specific cavities for the epitope. In this work two molecularly imprinted polymer formulations (a macroporous monolith and nanospheres) were obtained using the protected peptide Z-Thr-Ala-Ala-OMe, as template, and Z-Thr-Ile-Leu-OMe, as analogue for the selectivity evaluation, methacrylic acid, as functional monomer, and trimethylolpropane trimethacrylate and pentaerythritol triacrylate (PETRA), as cross-linkers. Polymers were synthesized by precipitation polymerization and characterized by standard techniques. Polymerization and rebinding solutions were analyzed by high performance liquid chromatography. The highly cross-linked polymers retained about 70% of the total template amount, against (20% for the less cross-linked ones). The extracted template amount and the rebinding capacity decreased with the cross-linking degree, while the selectivity showed the opposite behaviour. The PETRA cross-linked polymers showed the best recognition (MIP 2-, alpha=1.71) and selectivity (MIP 2+, alpha'=5.58) capabilities. The cytotoxicity tests showed normal adhesion and proliferation of fibroblasts cultured in the medium that was put in contact with the imprinted polymers.
Journal of Cellular and Molecular Medicine 11(6):1367-76. · 4.13 Impact Factor
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ABSTRACT: Polymers have widespread applications in therapeutics, and their use can play important structural and functional roles in different disease conditions. Bioartificial biodegradable materials, to be used as biomaterials and, in particular, as localized drug carriers, were prepared mixing chitosan (CHI) and poly(vinyl alcohol) (PVA), then manufactured as films, and finally cross-linked with glutaraldehyde (GTA), both in the absence and in the presence of the edible plasticizer sorbitol (SOR). The materials were characterized by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), ther-mogravimetric analysis (TGA), X-ray diffraction, scanning electron microscopy (SEM), and tensile test. The FTIR spectroscopy and the X-ray diffraction indicated that the presence of CHI lowers the crystallinity of PVA, and that the cross-linking with GTA does not modify the interactions between the two polymers, but only forms bridges between the different chains. In addition, the thermodynamic parameters for PVA, evaluated from the DSC measurements, confirmed that the PVA structure was less crystalline in the blends than in the pure state. The addition of SOR as a plasticizer to the CHI/PVA blends generally improved the characteristics of the films, making the cross-linked films less brittle, as confirmed by the SEM measurements and by the mechanical test. The TGA measurements confirmed the presence of chemical interactions between the polymers, as indicated by the DSC measurements. On the whole, the physicochemical properties of the blends showed the strong interactions existing between the component materials.
Journal of applied biomaterials & biomechanics (JABB) 5(3):184-91. · 0.76 Impact Factor
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ABSTRACT: Two ionomeric materials, cross-linked through the formation of polyoxyethylene bridges, were synthesized by the reaction of poly(styrene-alt-maleic anhydride) (PSMA) with poly(ethylene glycol) (PEG), carried out in the absence of external catalysts. The reaction was carried out at room temperature, both in bulk with excess glycol, and in acetone solution with a 20:1 ratio of anhydride rings to hydroxyl groups. The materials were characterized by scanning electron microscopy (SEM), total reflection Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The SEM showed a quite uniform porous structure for the material synthesized in bulk, and two distinct phases for that synthesized in acetone solution, a sponge-like structure and a denser one. The FTIR spectra showed that the first material underwent the cross-linking reaction to a greater extent than the second one. Both TGA and DSC confirmed the formation of cross-linked structures. Such tri-dimensional networks, owing to the presence of the carboxyl groups, could easily entrap either cationic drugs, in view of a possible controlled release, or poisonous metal cations, when they must be removed from blood. The second use can be made easier by the hemocompatibility, ascertained in preceding studies on other materials, synthesized by the reaction between maleic anhydride copolymers and hydroxyl-containing macromolecules. Another possible use is the production of ion exchanging gels, as fillers for both ion exchange and liquid chromatography columns, which could be easily regenerated.
Journal of applied biomaterials & biomechanics (JABB) 4(2):97-101. · 0.76 Impact Factor
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ABSTRACT: Ionizable hydrogels were prepared from new copolymers, poly(vinylalcohol-co-acrylic acid) indicated as P(VA-co-AA), by freezing-thawing processes. These materials are designed as potential controlled delivery devices with specific properties to respond to chemical environment stimuli. The swelling behavior of the P(VA-co-AA) hydrogels was evaluated in response to pH changes in release medium demonstrating a strong dependence with the environmental pH. The release of theophylline (THO) and bovine serum albumin (BSA) incorporated into the hydrogels before freezing-thawing cycles were examined by varying the pH. The release curves of the two different solutes showed a very similar trend depending on the hydrogel porosity and the medium pH. The dependence of THO and BSA release on their size and ionic nature was detected.
Journal of applied biomaterials & biomechanics (JABB) 4(1):31-7. · 0.76 Impact Factor
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ABSTRACT: Bioartificial membranes of synthetic (poly(ethylene-co-vinyl alcohol) - EVAL, Clarene (R) ) and biological (dextran) polymers with different compositions were prepared through the phase inversion process. Dimethyl sulfoxide (DMSO) solutions of EVAL and dextran were mixed under stirring in the desired proportions and coagulated in water or DMSO (solvent)/water (non-solvent) mixture. Membrane morphologies were shown to be dependent on the synthetic and biological polymer contents and on the coagulation medium composition. Component release during solid membrane formation was evaluated by a UV method and the final composition of the bioartificial membranes established, confirming the successful entrapment of the biological component in the synthetic network. The porosity degree of the bioartificial membranes was also investigated by permeability tests and the effect of morphological characteristics on transport properties was studied. Water flux across the membranes, solute permeability and sieving coefficients were also calculated. The results revealed that the transport properties of these bioartificial membranes, obtained by the phase inversion method, could be controlled by mainly changing the preparation control parameters and the EVAL-dextran ratio.
Journal of applied biomaterials & biomechanics (JABB) 3(2):83-92. · 0.76 Impact Factor
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ABSTRACT: Therapeutic approaches in the clinical field require advanced properties for delivery or recognition of clinical species. The molecular imprinting method allows selective cavities to be inserted into a polymeric material built "around" a stamp molecule (template) through polymerization or phase inversion. This study focuses on the application of both methods in the realization of polymeric membranes with selective recognition and adsorption properties. Imprinted polymethacrylic acid (PMAA) particles, exhibiting specific binding sites for cholesterol molecule (template), were realized via precipitation polymerization in the shape of nanobeads and loaded in the bulk or on the surface of methylmethacrylate-acrylic acid P(MMA-co-AA) membranes obtained by the non-solvent induced phase separation (NIPS) technique. In this way, specific cavities were introduced into the membrane network to enhance and specialize uptake performances of the porous membranes taking advantage of the particle characteristics. Rebinding performances towards cholesterol in a physiological environment were tested showing very interesting results: the adsorption of cholesterol molecules from physiological solution was increased by using composite membrane-nanobead systems instead of control membranes (a quantitative increase of 14 mg of cholesterol per g of polymer matrix in respect of blank membrane was detected). The results obtained showed an improved performance of composite membranes, but also an unmodified behavior of loaded nanobeads (with respect to free ones) concerning the recognition capability in aqueous medium, which is the most difficult obstacle to overcome in molecular imprinting. The absolute rebinding capacity and the imprinting efficiency of membranes were in the range (and in some case higher) of other efficient systems, but the real improvement was that molecularly imprinted embranes showed an excellent recognition capacity in physiological medium instead of organic solvents.
Journal of applied biomaterials & biomechanics (JABB) 5(3):166-75. · 0.76 Impact Factor
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ABSTRACT: Most of the systems developed for controlled drug delivery applications depend on membrane technology and their preparation parameters. For some applications, a dense membrane structure used in controlled-release systems can excessively prolong drug release due to the low permeability of the coating to the drug or to the low solubility of the drug in water. In these cases, to increase the drug delivery rate, asymmetric membranes can be prepared by a phase-inversion technique, allowing a different drug delivery approach with respect to dense membranes. In this study, porous poly(methyl methacrylate) membranes with different vacuum degrees were prepared through the phase-inversion process. Ternary homogeneous solutions, obtained by mixing polymer, tetrahydrofuran (THF) and water in the desired amounts, were precipitated by the evaporation of a solvent (THF) and a non-solvent (water) at a controlled temperature and ventilation. Membrane morphology, investigated by scanning electron microscopy, showed it to have a diffuse porosity with a regular arrangement and geometry of pores on the top surface. The porosity degree of the membranes, mainly relying on the starting polymer concentration, was also investigated by the use of the software Image-Pro Plus, indicating the presence of a relationship between porosity and permeability characteristics. Membranes, containing folic acid as a model drug, were tested for their transport characteristics and drug delivery both in diffusive and in convective- diffusive conditions. Transport and release parameters, as well as permeability and effective diffusivity, were found to be dependent on the porosity and vacuum degree, which could be controlled by varying the preparation conditions. Furthermore, these membranes showed high hydraulic permeability and rapid drug release, suggesting their use for applications where an intensive therapy in the first few days is required, followed by a constant and slow release for a longer time (two-step drug delivery).
Journal of applied biomaterials & biomechanics (JABB) 5(2):95-106. · 0.76 Impact Factor
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ABSTRACT: Molecular imprinting permits to introduce in synthetic macromolecules molecular information through the polymerisation of a monomer in the presence of a stamp molecule (template): the solution polymerisation is receiving, in the last 5 years, increasing attention due to the effective selective behaviour of produced materials obtained in the shape of micro or nanoparticles. The frontier of this family of materials is the improvement of recognition performances in aqueous environment. Our work started from the idea to increase binding and selective behaviour of cross-linked poly(methylmethacrylate-co-methacrylic acid) nanospheres in aqueous media through an innovative approach: imprinted nanospheres are loaded in the bulk or on the surface of poly(methylmethacrylate-co-acrylic acid) membranes. In this way, enhanced recognition performances of acrylic membranes can be expected, taking advantage of recognition characteristics of imprinted nanospheres. Recognition and binding behaviour of free and supported particles was compared, showing an increased recognition factor for loaded particles. Imprinted particles were able to keep-on 1.72 mg of theophylline and 4.12 mg of caffeine/g of polymer in physiological solution and the recognition factors for each template resulted to be higher for supported particles, in particular in the case of theophylline (passing from 1.02 to 6.32), suggesting the creation of a preferred microenvironment for the rebinding of nanoparticles.
Analytica Chimica Acta.
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ABSTRACT: Bioartificial polymeric materials based on blends of dextran and poly(vinyl alcohol-co-acrylic acid) P(VA-co-AA) were prepared in the form of films and characterised to evaluate the miscibility of the natural component with the synthetic one. The idea of this work was to compatibilise PVA and dextran by introducing carboxylic groups along the PVA chains.The copolymer was synthesised and characterised in our laboratories. The results evidenced that the copolymer had an appropriate molecular weight and the content of PAA in the copolymer was 45% (weight). Then, films with different composition ratios were prepared by solution casting and analysed by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), chemical imaging analysis and mechanical tests. The results obtained indicated that the introduction of carboxylic groups along the PVA chains had a positive effect on the miscibility degree of the synthetic component with the biological one.
European Polymer Journal.
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ABSTRACT: Membranes with molecular recognition properties were obtained by coagulation in the presence of compounds of biotechnological interest or by modification of non-imprinted membranes with the introduction of imprinted nanoparticles obtained by polymerisation of a monomer(s) in the presence of a stamp molecule (template). The functional binding performances in aqueous medium towards template molecules (uric acid, theophylline, caffeine or proteins) were investigated.Membranes of acrylonitrile-acrylic acid copolymer imprinted with uric acid showed satisfactory recognition capacity and selectivity towards the template (rebinding of uric acid resulted 2.4 times higher than that of theophylline). Porous supports of ethylene-co-vinyl alcohol-dextran blends were obtained using α-amylase as template and selective properties were confirmed by a rebinding of the stamp molecule 1.96 times higher than that of albumin. In some cases, recognition properties of methylmethacrylate-co-acrylic acid membranes were enhanced by loading on the surface, or inside the membrane, imprinted cross-linked methylmethacrylate-methacrylic acid nanospheres. The different membranes realised are promising solutions for filtration or adsorption applications in biomedical field or for other biotechnological uses where biomimetic behaviour in water media is requested.
Journal of Membrane Science.
