Temperature-sensitive aqueous microgels.

Functional polymer microspheres

The last decade of research in the physical sciences has seen a dramatic increase in the study of nanoscale materials. Today, "nanoscience" has emerged as a multidisciplinary effort, wherein obtaining a fundamental understanding of the optical, electrical, magnetic, and mechanical properties of nanostructures promises to deliver the next generation of functional materials for a wide range of applications. While this range of efforts is extremely broad, much of the work has focused on "hard" materials, such as Buckyballs, carbon nanotubes, metals, semiconductors, and organic or inorganic dielectrics. Meanwhile, the soft materials of current interest typically include conducting or emissive polymers for "plastic electronics" applications. Despite the continued interest in these established areas of nanoscience, new classes of soft nanomaterials are being developed from more traditional polymeric constructs. Specifically, nanostructured hydrogels are emerging as a promising group of materials for multiple biotechnology applications as the need for advanced materials in the post-genomic era grows. This review will present some of the recent advances in the marriage between water-swellable networks and nanoscience.

Soft nanotechnology with soft nanoparticles.

Secretory cells contain submicroscopic granules composed of a polyanionic polymer network that is collapsed owing to the presence of hydronium ions and weak base cations. The network is encapsulated within a lipid membrane, and functions as a vehicle for the osmotically inert storage of a variety of granule-bound endogenous mediator species, such as histamine, serotonin and proteases. These species are excreted from the granule and thence from the cell in response to external biochemical signals. Hydrogels that swell and shrink in response to external stimuli might serve as synthetic analogues of secretory granules. Here we describe the systematic engineering of multi-component, environmentally responsive hydrogel microspheres, coated with a lipid bilayer to mimic more closely the natural secretory granule. These microspheres exhibit pH- and ion-dependent volume phase transitions and ion-sensitive exchange of bound cations when the encapsulating lipid membrane is porated. We stimulated poration electrically in individual microgel particles immobilized and manipulated with a micropipette. This system could find use for the triggered release of encapsulated drugs in the body.

A synthetic mimic of the secretory granule for drug delivery

The pH and NaCl induced swelling response and drug and protein loading of poly(methacrylic acid-co-acrylic acid) microgels (4−10 μm diameter) were measured as a function of cross-link density. The swelling ratio (Q) of the microgels increased linearly from 2 to 12 when the mole fraction of cross-linking monomer decreased from 0.25 to 0.10 (at pH's > 5.3). In the presence of 5 M NaCl (at pH's > 5.3), microgels with cross-linking feed ratios of 0.25 and 0.10 swelled to only 80% and 60% of their maximum volume measured at low ionic strength, respectively. To determine the average pore size in the different cross-linking density microgels (feed ratios = 0.25, 0.20, 0.15, and 0.10), we measured the size cutoffs for the uptake of different sized proteins. On the basis of these size exclusion experiments, we calculated the number of monomers between cross-links in each of these gels to be 6.5, 9.5, 12.5, and 16.5, respectively. These values were used in our theoretical modeling of the network swelling (modified ...

Investigation of the Swelling Response and Loading of Ionic Microgels with Drugs and Proteins: The Dependence on Cross-Link Density

Monodisperse, reactive hydrogel microspheres were prepared by precipitation polymerization ofp-nitrophenyl acrylate (NPA) with acrylamide, methacrylic acid, and methylenebisacrylamide in ethanol. The size of microspheres was controlled by the monomer ratio. Some fraction of reactive ester decomposed during the polymerization. The reactive hydrogel microspheres were converted to amphoteric ones by the reaction of NPA units with diamine. The isoelectric point of the amphoteric microspheres was around 4.0, but it was different from the pH at which the microspheres have the minimum size or the most shrunken state. This was attributed to the uneven distribution of induced amine groups.

Preparation of monodisperse, reactive hydrogel microspheres and their amphoterization

Poly(N-isopropylacrylamide) (PNIPAM) hydrogel microspheres were prepared by precipitation polymerization above the polymer's LCST in water. The hydrodynamic size of PNIPAM microspheres exhibited a thermo-sensitive change around the LCST. In order to obtain information about the interface of the hydrogels, contact angle measurement, protein adsorption, and fluorescence analysis were performed. The results led to the conclusion that the surface of the thermosensitive hydrogel microsphere become hydrophobic above the LCST in conjunction with its volume transition. This can be explained by association of segments induced by the hydrophobic interaction above the LCST.

M. Kashiwabara

Papers

Preparation of monodisperse, reactive hydrogel microspheres and their amphoterization

Fluorescence analysis for thermo‐sensitive hydrogel microspheres