124 research outputs found
A study of thermoassociative gelation of aqueous cationic poly(N-isopropyl acrylamide) graft copolymer solutions
No full textIn this work thermoassociative gel formation of a new family of aqueous temperature-responsive copolymer solutions has been investigated. This was achieved using a cationic poly(N-isopropyl acrylamide) (PNIPAm) graft copolymer recently prepared [Liu R, De Leonardis P, Cellesi F, Tirelli N, Saunders BR. Langmuir 2008;24:7099]. The PDMA+x-g-(PNIPAmn)y copolymers have x and y values that originate from the macroinitiator; the value for n corresponds to the PNIPAm arm length. DMA+ is quarternarized N,N-dimethylaminoethyl methacrylate. The copolymer solutions exhibited cloud point temperatures (Tclpt) of about 33 °C, which were not significantly affected by x/y ratio or the value for n. Thermoassociative gel formation occurred above Tclpt at copolymer concentrations (Ccopol) greater than or equal to 4 wt.%. This is a reasonably low Ccopol value and is a consequence of the graft copolymer architecture employed. We investigated the effect of temperature, Ccopol and copolymer structure on gelation and gel elasticity using variable - temperature dynamic rheology. For PDMA+30-g-(PNIPAm210)14 solutions at 39 °C it was found that G′ (elastic modulus) scales with Ccopol according to G′ ∼ Ccopol3.85. The data suggested that a significant proportion of PNIPAm units is not directly involved in network formation. Thermoassociative gel formation and the gel properties for these systems appear to be governed by a balance between electrostatic repulsion involving the DMA+ units (favouring spatial extension of the copolymer backbones) and attractive hydrophobic interactions between PNIPAm side chains (favouring associative crosslink formation). © 2009 Elsevier Ltd. All rights reserved
Intracellular delivery of therapeutic proteins. New advancements and future directions
No full textAchieving the full potential of therapeutic proteins to access and target intracellular receptors will have enormous benefits in advancing human health and fighting disease. Existing strategies for intracellular protein delivery, such as chemical modification and nanocarrier-based protein delivery approaches, have shown promise but with limited efficiency and safety concerns. The development of more effective and versatile delivery tools is crucial for the safe and effective use of protein drugs. Nanosystems that can trigger endocytosis and endosomal disruption, or directly deliver proteins into the cytosol, are essential for successful therapeutic effects. This article aims to provide a brief overview of the current methods for intracellular protein delivery to mammalian cells, highlighting current challenges, new developments, and future research opportunities
Tuning the properties of hybrid SiO2/ poly(glycerol monomethacrylate) nanoparticles for enzyme nanoencapsulation
No full textWe explored a versatile enzyme nanoencapsulation process based on the synthesis of silica gel nanoparticles, decorated with a dense hydrophilic poly(glycerol monomethacrylate) (PGMMA) shell for biological and therapeutic applications. These hybrid enzyme-SiO2-polymer nanoparticles were obtained through an aqueous solgel process, followed by the adsorption of cationic macroinitiators by electrostatic complexation. Surface-initiated Atom Transfer Radical Polymerisation (ATRP) was applied to obtain a dense hydrophilic (protein repellent) PGMMA layer of tunable size, under conditions which are compatible with the nanoencapsulation of horseradish peroxidase. The sol-gel synthetic procedure, the composition and molecular weight of the macroinitiators, the polymer adsorption and purification methods, and the final ATRP conditions, were optimised to control the properties of these nanoparticles, in terms of particle size, Z-potential, PGMMA decoration, while preserving enzymatic activity
A new process for cell microencapsulation and other biomaterial applications: Thermal gelation and chemical cross-linking in “tandem”
No full textThe very rapid gelation of a cell- or biomolecule-containing solution is at the basis of most processes employed in microencapsulation. Adequately quick ('instantaneous') gelation kinetics are provided by a number of phenomena based on physical association. On the other hand, physical gels are inherently reversible structures, which can be solubilized or disrupted in response to often poorly controllable phenomena in the environment of application, such as dilution, changes in temperature, ion strength and composition, pH, or other physical or chemical parameters. Chemically cross-linked hydrogels would have therefore significant advantages in terms of stability and end-properties; however, the time required for chemical reactions to produce a chemically cross-linked material is in a more general case hardly compatible with microencapsulation processes. In a recent study of our laboratory we have proposed a new approach for providing both quick gelation kinetics and good stability, by simply combining the rapid kinetics of a physical hardening phenomenon with a slower chemical curing; the former process is thus responsible of the morphogenesis of the material, while the latter develops its end-properties. © 2005 Springer Science + Business Media, Inc
Sol–gel synthesis at neutral pH in W/O microemulsion: A method for enzyme nanoencapsulation in silica gel nanoparticles
No full textThe classical sol-gel synthesis of silica gels has been adapted to a W/O (micro)emulsion process under conditions that minimize denaturing effects on encapsulated enzymes. We have in particular focused on optimizing the purification procedures with the aim to produce water nanoparticles dispersions from W/O emulsions without the use of precipitation/sedimentation steps. A proof of principle of encapsulation has been conducted using horseradish peroxidase (HRP). Crown Copyright © 2006
F NMR Detection
No full textIn the continuous search to develop multimodal systems with combined diagnostic and therapeutic functions, several efforts have been focused on the development of multifunctional drug delivery systems. Herein we designed, by a covalent approach, a novel class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) containing an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F 3 -PLGA and F 9 -PLGA, were synthesized and their chemical structure and thermal stability were analysed by solution NMR, DSC, and TGA. The obtained F-PLGA compounds were proved to form in aqueous solution colloidal stable nanoparticles (NPs) displaying a strong 19 F-NMR signal. The fluorinated NPs also showed an enhanced ability to load hydrophobic drugs containing fluorine atoms with respect to analogue pristine PLGA NPs. Preliminary in vitro studies showed their cellular availability and ability to intracellularly deliver and release a functioning drug
FLUORINATED HYPERBRANCHED POLYGLYCEROL POLYMERS AND CORRESPONDING NANOPARTICLES AND ENCAPSULANTS Fluorinated hyperbranched polyglycerol polymers and corresponding nanoparticles and encapsulants
No full textAGET ATRP of Poly[poly(ethylene glycol) methyl ether methacrylate] Catalyzed by Hydrophobic Iron(III)-Porphyrins
No full textCommercially available hydrophobic porphyrins are investigated as an environmentally friendly catalytic system for iron-mediated atom transfer radical polymerization (ATRP) of poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). Polymerizations in organic solvent are optimized using activators generated by electron transfer (AGET ATRP), based on iron(III)-porphyrin complexes, and tin(II) 2-ethyl hexanoate or ascorbic acid as a reducing agent. Copper-free PPEGMA macromolecules are obtained with high conversion, controlled molecular weight, and polydispersity index compared with standard copper-based ATRP. The facile preparation and availability of the catalyst, together with its expected low toxicity, represent clear advantages for the synthesis of PPEGMA-based materials for biomedical use
Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies
No full textThe impact of protein therapeutics in healthcare is steadily increasing, due to advancements in the field of biotechnology and a deeper understanding of several pathologies. However, their safety and efficacy are often limited by instability, short half-life and immunogenicity. Nanodelivery systems are currently being investigated for overcoming these limitations and include covalent attachment of biocompatible polymers (PEG and other synthetic or naturally derived macromolecules) as well as protein nanoencapsulation in colloidal systems (liposomes and other lipid or polymeric nanocarriers). Such strategies have the potential to develop next-generation protein therapeutics. Herein, we review recent research progresses on these nanodelivery approaches, as well as future directions and challenges
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