We report investigations on the thermally regulated uptake and release of the chemotherapeutic drug doxorubicin from microgel thin films. A spin coating, layer-by-layer (scLbL) assembly approach was used to prepare thin films composed of thermoresponsive poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-AAc) microgels by alternatively exposing a 3-aminopropyltrimethoxysilane (APTMS) functionalized glass substrate to polyanionic pNIPAm-AAc microgels and polycationic poly(allylamine hydrochloride) (PAH). Using this method, 10, 20, and 30 microgel layer films were constructed with uniform layer buildup, as confirmed by quartz crystal microgravimetry (QCM). The films were subsequently loaded with doxorubicin by cycling the temperature of the film in an aqueous doxorubicin solution between 25 and 50 degrees C. Release characteristics were then examined using UV-vis spectroscopy, which revealed temperature-dependent release properties.
We describe investigations of thermally triggered insulin release from poly(N-isopropylacrylamide-co-acrylic acid) microgel thin films prepared by layer-by-layer (LbL) polyelectrolyte assembly. The thermoresponsivity of these films was confirmed using light scattering techniques. Simultaneous monitoring of film collapse and insulin release kinetics shows that deswelling of the films is partially decoupled from macromolecule release and that release is mainly governed by partitioning effects. We hypothesize, however, that film thermoresponsivity plays an important role in that subjection to many thermal cycles enables the embedded peptide to solubilize and subsequently partition through film layers. Direct pulsatile and extended release studies confirm the capability of these films to release bursts of insulin over many cycles, and confirm that the magnitude of the release can be controlled based on film thickness. These insulin-impregnated films are extremely stable with the potential to release constant pulses of peptide for more than 1 month at a time.
Thermoresponsive poly(N-isopropylacrylamide) (pNIPAm) microgel particles cross-linked with various concentrations of PEG diacrylates of 3 different PEG chain lengths were synthesized via free-radical precipitation polymerization in order to investigate the phase transition and protein adsorption behavior as the hydrophilicity of the network is increased. Photon correlation spectroscopy (PCS) reveals that, as the concentration of PEG cross-linker incorporated into the particles is increased, an increase in the temperature and breadth of the phase transition occurs. Qualitative differences in particle density using isopycnic centrifugation confirm that higher PEG concentrations result in denser networks. The efficient incorporation of PEG cross-linker was confirmed with (1)H NMR, and variable temperature NMR studies suggest that, in the deswollen state, the longer PEG cross-links protrude from the dense globular network. This behavior apparently manifests itself as a decrease in nonspecific protein adsorption with increasing PEG length and content. Furthermore, when electrostatically attached to a glass surface, the particles containing the longer chain lengths exhibited enhanced nonfouling behavior and were resistant to cell adhesion in serum-containing media. The excellent performance of these particulate films and the simplicity with which they are assembled suggests that they may be applicable in a wide range of applications where nonfouling coatings are required.
We describe investigations of insulin release from thermoresponsive microgels using variable temperature (1)H NMR. Microgel particles composed of poly(N-isopropylacrylamide) were loaded with the peptide via a swelling technique, and this method was compared to simple equilibrium partitioning. Variable temperature (1)H NMR studies suggest that the swelling loading method results in enhanced entrapment of the peptide versus equilibrium partitioning. A centrifugation-loading assay supports this finding. Pseudo-temperature jump (1)H NMR measurements suggest that the insulin release rate is partially decoupled from microgel collapse. These types of direct release investigations could prove to be useful methods in the future design of controlled macromolecule drug delivery devices.
We describe studies concerning the construction and characterization of insulin‐impregnated poly(N‐isopropylacrylamide‐co‐acrylic acid) microgel thin films prepared by Layer‐by‐Layer (LbL) polyelectrolyte assembly. These films can be built up in a highly uniform fashion and display linear buildup dependence even up to 30 layers. Thermoresponsivity of these drug loaded films can be utilized to obtain extended pulsatile release of insulin over many cycles. Continuous thermal pulsing allows solubilization of the embedded peptide and subsequent diffusion through the film layers. The magnitude of release can be tuned based on film thickness. This type of microgel thin film construct proves to be extremely robust and can potentially pulse out constant bursts of peptide for more than one month at a time.
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