Poly(N-isopropylacrylamide-co-N-vinylpyrrolidone) thermoresponsive microspheres: The low drug loading ensures the pulsatile release mechanism

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Membrane emulsification for the production of uniform poly-N-isopropylacrylamide-coated alginate particles using internal gelation

Alginate particles, crosslinked by calcium ions, have a number of potential biopharmaceutical industry applications due to the biocompatibility of the materials used and formed. One such use is as microcarriers for cell attachment,growth and then detachment without the use of proteolytic enzymes. A straightforward and reproducible method for producing uniform calcium alginate particles with controllable median diameters which employs membrane emulsification and internal gelation (solid particles contained in the dispersed phase) is demonstrated, as well as functionalisation of the resulting beads with amine terminated poly N-isopropylacrylamide (pNIPAM) to form temperature responsive particles, by taking advantage of the electrostatic interaction between the carboxyl groups of the alginate and amino groups of the modified pNIPAM. Cell attachment, growth and detachment capabilities of these core–shell structures were assessed and successfully demonstrated by using phase contrast microscopy and fluorescent staining with calcein-AM and ethidium homodimer-1.The formulation used for the alginate particles avoided non-GRAS chemicals by only using food grade and pharmaceutical grade reagents. The median particle size was controllable within the range between 55 m and 690 m and the size distributions produced were very narrow: ‘span’ values as low as 0.2. When using a membrane pore sizeof 20 m no membrane blockage by the suspended calcium carbonate necessary for internal gelation of the alginate particles was observed. Membrane pore openings with diameters of 5 and 10 m were also tested, but blocked with the 2.3 m median diameter calcium carbonate solids

Влияние строения катионных сомономеров на термочувствительность их сополимеров с N-изопропилакриламидом в водных растворах

Методами статического и динамического рассеяния света исследовано поведение в разбавленных водных растворах сополимера N-изопропилакриламида с метакриловой кислотой в широком интервале температур. Показано, что структурно-фазовый переход, наблюдаемый с повышением температуры в растворах сополимера, происходит в более низкотемпературной области и более узком интервале температур, чем в растворе той же концентрации и рН сополимера N-изопропилакриламида с малеиновой кислото

Aminated polysaccharide microspheres as DNA delivery systems

This paper describes the production and characterization of cationic microparticles based on pullulan and starch for the delivery of nucleic acids.The microparticles were prepared by chemically cross-linkinking of a polymer solution dispersed in organic phase, followed by amination with N, N-diethyl-2-chloroethyl amine hydrochloride or N-glycidyl-N, N-dimethyl-N-methylammonium chloride. The association of desoxyribonucleotide Defibrotide (DFT) with positively charged microparticles was determined. The association capacity and the affinity of microspheres for DFT were investigated as a function of type of polysaccharide, content and basicity of the aminogroups. It was found that the both types of carriers synthetized display a high affinity for Defibrotide due to the high porosity of polysaccharide microspheres. In addition, the in vitro release kinetics from microspheres were determined

Preparation and characterization of pH- and temperature-sensitive pullulan microspheres for controlled release of drugs

Most part of pH- and temperature-sensitive microspheres used for the controlled delivery of drugs are not biodegradable. Therefore, the aim of this work is to prepare pH- and temperature-sensitive microspheres from biodegradable and biocompatible natural polymers. Pullulan microspheres were prepared by suspension cross-linking with epichlorohydrin of an aqueous solution of the polymer. In order to confer them temperature sensitivity, poly(N-isopropylacrylamide-co-acrylamide) was grafted onto pullulan microspheres. Then, the pH-sensitive units (–COOH) were introduced by reaction between the remaining –OH groups of the pullulan with succinic anhydride. The grafted pullulan microspheres are more hydrophilic than pullulan microspheres, their swelling degree as well as water regain increase significantly. The thermo-sensitivity of the carboxylated microspheres depends to the number and the ionization form (–COOH/–COO) of carboxylic groups. At a low exchange capacity (0.35 meq/g), microspheres are thermo-sensitive both in the protonated and deprotonated form of –COOH groups. At a higher exchange capacity (2.25 meq/g), microspheres are almost unswellable in the protonated form and swell extensively in the ionized form (up to 28 times than their dried form) loosing in a great extent the thermo-sensitive properties. In isotonic phosphate buffer pH ¼ 7.4, both thermo-sensitive and pH/ thermo-sensitive microspheres possess a phase transition temperature close to that of the human body temperature. Loading and release profiles of lysozyme, taken as a molecular model system, were investigated