The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. Although numerous protein antigens have been identified that can generate immunity to infectious pathogens, the development of vaccines based on protein antigens has had limited success because of delivery issues. In this article, an acid-sensitive microgel material is synthesized for the development of protein-based vaccines. The chemical design of these microgels is such that they degrade under the mildly acidic conditions found in the phagosomes of antigenpresenting cells (APCs). The rapid cleavage of the microgels leads to phagosomal disruption through a colloid osmotic mechanism, releasing protein antigens into the APC cytoplasm for class I antigen presentation. Ovalbumin was encapsulated in microgel particles, 200 -500 nm in diameter, prepared by inverse emulsion polymerization with a synthesized acid-degradable crosslinker. Ovalbumin is released from the acid-degradable microgels in a pH-dependent manner; for example, microgels containing ovalbumin release 80% of their encapsulated proteins after 5 h at pH 5.0, but release only 10% at pH 7.4. APCs that phagocytosed the acid-degradable microgels containing ovalbumin were capable of activating ovalbumin-specific cytoxic T lymphocytes. The aciddegradable microgels developed in this article should therefore find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity.polymer ͉ crosslinker ͉ encapsulation ͉ vaccination ͉ cytotoxic T lymphocyte

A broad variety of monolithic macroporous polymers with both controlled chemistry and porous properties was prepared using UV‐initiated free‐radical polymerization. The chemistry of the monoliths is defined by the composition of the monomer mixture used for the polymerization. The use of functional methacrylate monomers such as glycidyl methacrylate, 2‐hydroxyethyl methacrylate, butyl methacrylate, 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid, and [2‐(methacryloyloxy) ethyl] trimethylammonium chloride enabled the preparation of monoliths with reactive, hydrophilic, hydrophobic, and ionizable functionalities, respectively. The porous properties of these monoliths were mainly affected by the choice of the porogenic solvent system. Because the UV polymerization was carried out at room temperature, even low molecular weight alcohols and other low boiling point solvents could safely be used to create a versatile series of binary porogenic mixtures. Monoliths were prepared in spatially defined positions using the photolithographic technique within a fused silica capillary and on microfluidic chips, and the former was demonstrated with the separation of derivatized amines by means of capillary electrochromatography in the reversed‐phase mode. Similarly, a monolith prepared in the microchip format was used to demonstrate a microextraction with enrichment of a solution of green fluorescent protein by a factor of 1000. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 755–769, 2002; DOI 10.1002/pola.10155

Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polymerization in an inverse emulsion system. Acrylamide-based microspheres 0.2-1 microm in diameter were prepared using an acid-cleavable difunctional monomer. Retention of the DNA payload at physiological pH with complete release under acidic conditions at lysosomal pH was demonstrated. By trapping the plasmid DNA within the cross-linked microparticle, enzymatic degradation was prevented when exposed to serum nucleases. For vaccine development, these delivery vehicles were also investigated for their ability to generate immune responses when delivered to phagocytic cells of the immune system. Encapsulated plasmid DNA demonstrated immunostimulatory activity in macrophages, leading to cytokine secretion of IL-6 with a response approximately 40-fold higher than that achieved with DNA alone.

The effect of variables such as shape template size, porogen composition and percentage, content of cross-linking monomer, and polymerization temperature on the properties of uniformly sized 3-microm porous poly(glycidyl methacrylate-co-ethylene dimethacrylate) beads prepared by the staged templated suspension polymerization technique has been studied. The porous properties of the beads including surface morphology, pore size distribution, and specific surface area have been optimized to obtain highly efficient stationary phases for normal-phase HPLC. A column packed with diol stationary phase obtained by hydrolysis of poly(glycidyl methacrylate-co-ethylene dimethacrylate) beads affords an efficiency of 67,000 plates/m for toluene using THF as the mobile phase. The retention properties and selectivity of the diol beads are easily modulated by changes in the composition of the mobile phase. The performance of these beads is demonstrated with the separations of a variety of polar compounds including positional isomers, aniline derivatives, and basic tricyclic antidepressant drugs.

Novel chiral stationary phases (CSP) have been prepared by coating the internal surface of monodisperse macroporous poly(2-aminoethyl methacrylate-co-ethylene dimethacrylate) beads with dimethylphenylcarbamate derivatives of regenerated cellulose. The coating was achieved either by simple adsorption or by chemical bonding using a diisocyanate linker. Separation of enantiomers in normal-phase HPLC mode was used to evaluate the enantioselectivity of all CSPs. The influence of the properties of the polymer support such as pore size, pore volume, and content of the amine functionalities, reaction and separation conditions such as weight ratio of modified cellulose selector to polymer beads, amount of diisocyanate crosslinker, and the composition of the mobile phase on chiral discrimination and chromatographic resolution were also systematically investigated. The CSPs prepared by chemical anchoring were more stable and a wider range of solvents including dichloromethane could be used for the separations. Compared to the coated-type CSPs, the chemically bonded stationary phases enabled the enantioseparations of a larger number of racemates and exhibited enantioselectivity fully comparable to their counterparts prepared using porous silica as a support. However, the benefits of tailored macroporous polymer supports demonstrated earlier with brush-type CSPs did not enhance the performance of the chiral stationary phases prepared from cellulose-based selectors.

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Synthesis of pyrazole-3-carboxylic acid was progressed via two different protocols, one of which is solid state. Pyrazole-3-carboxylic acid was converted into different derivatives such as ester, urea, amide and nitrile. The amide compound was converted to nitrile using SOCl2 and DMF. Solid state heating of carboxylic acid gave decarboxylated product. Cyclization of tetra-substituted pyrazole with hydrazines resulted in pyrazolopyridazinones. The antimicrobial activities of the synthesized pyrazole derivatives against Bacillus cereus, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, and Saccharomyces cerevisiae were evaluated. One of the pyrazole derivatives which possess nitro group showed antimicrobial activity in only B. cereus, a Gram-positive bacteria, with an MIC of 128 μg/mL.