Myung Han Lee

Enhanced release of small molecules from near-infrared light responsive polymer-nanorod composites.

Stimuli-responsive materials undergo structural changes in response to an external trigger (i.e., pH, heat, or light). This process has been previously used for a range of applications in biomedicine and microdevices and has recently gained considerable attention in controlled drug release. Here, we use a near-infrared (NIR) light responsive polymer-nanorod composite whose glass transition temperature (T(g)) is in the range of body temperature to control and enhance the release of a small-molecule drug (<800 Da). In addition to increased temperature and resulting changes in molecule diffusion, the photothermal effect (conversion of NIR light to heat) adjusts the composite above the T(g). Specifically, at normal body temperature (T < T(g)), the structure is glassy and release is limited, whereas when T > T(g), the polymer is rubbery and release is enhanced. We applied this heating system to trigger release of the chemotherapeutic drug doxorubicin from both polymer films and microspheres. Multiple cycles of NIR exposure were performed and demonstrated a triggered and stepwise release behavior. Lastly, we tested the microsphere system in vitro, reporting a ∼90% reduction in the activity of T6-17 cells when the release of doxorubicin was triggered from microspheres exposed to NIR light. This overall approach can be used with numerous polymer systems to modulate molecule release toward the development of unique and clinically applicable therapies.

Microfluidic fabrication of stable nanoparticle-shelled bubbles.

We introduce a microfluidic approach to generating monodisperse, stable nanoparticle-shelled bubbles using air-in-oil-in-water (A/O/W) compound bubbles as templates. The oil phase of the A/O/W compound bubbles comprises a volatile organic solvent and a hydrophobic silica nanoparticle. Upon evaporation of the organic solvent, the nanoparticles in the oil layer form a stiff shell at the air-water interface, which drastically enhances the stability of the bubbles against dissolution and coarsening. On the basis of this approach, we demonstrate that it is also possible to generate functional bubbles stabilized by composite shells that are composed of mixtures of hydrophobic materials and nanoparticles with unique properties.

Combined Passive and Active Microrheology Study of Protein-Layer Formation at an Air—Water Interface

We investigate the mechanical properties of layers of the protein beta-lactoglobulin during their formation at the air-water interface using a combination of passive and active microrheological techniques. The passive microrheology, which employs multiple particle tracking measurements using spherical colloids, indicates that the interfacial rheology evolves over time through three stages as protein adsorbs at the interface: (i) an increase in viscosity, (ii) a period of spatial heterogeneity in which the interface contains elastic and viscous regions, and (iii) the development of a uniformly rigid elastic film. Varying solution pH between pH = 5.2, the isoelectric point of beta-lactoglobulin, and pH = 7.0 has no qualitative effect on this mechanical evolution. The active microrheology, which employs ferromagnetic nanowires rotating in response to magnetic torques, similarly shows an increasing interfacial viscosity at early times and evidence of mechanical heterogeneity at intermediate times. However, at late times, the nanowire mobility becomes strongly pH dependent. For pH = 5.2, the layer responds as a rigid elastic film to the stress imposed by the wire. For pH = 7.0, it displays a viscous response that contrasts with the passive measurements. We associate this contrast with a nonlinear response to the wire at late times that reflects a low yield stress of the film at higher pH. This ability to compare passive and active measurements demonstrates the advantage of applying multiple microrheological methods to resolve ambiguity in any single approach.

Tunable Hydrogel-Microsphere Composites that Modulate Local Inflammation and Collagen Bulking

Injectable biomaterials alone may alter local tissue responses, including inflammatory cascades and matrix production (e.g. stimulatory dermal fillers are used as volumizing agents that induce collagen production). To expand upon the available material compositions and timing of presentation, a tunable hyaluronic acid (HA) and poly(lactide-co-glycolide) (PLGA) microsphere composite system was formulated and assessed in subcutaneous and cardiac tissues. HA functionalized with hydroxyethyl methacrylate (HeMA) was used as a precursor to injectable and degradable hydrogels that carry PLGA microspheres (~50 μm diameter) to tissues, where the HA hydrogel degradation (~20 or 70 days) and quantity of PLGA microspheres (0-300 mgml(-1)) are readily varied. When implanted subcutaneously, faster hydrogel degradation and more microspheres (e.g. 75 mgml(-1)) generally induced more rapid tissue and cellular interactions and a greater macrophage response. In cardiac applications, tissue bulking may be useful to alter stress profiles and to stabilize the tissue after infarction, limiting left ventricular (LV) remodeling. When fast degrading HeMA-HA hydrogels containing 75 mgml(-1) microspheres were injected into infarcted tissue in sheep, LV dilation was limited and the thickness of the myocardial wall and the presence of vessels in the apical infarct region were increased ~35 and ~60%, respectively, compared to empty hydrogels. Both groups decreased volume changes and infarct areas at 8 weeks, compared to untreated controls. This work illustrates the importance of material design in expanding the application of tissue bulking composites to a range of biomedical applications.

Elastic instability of polymer-shelled bubbles formed from air-in-oil-in-water compound bubbles

We study the stability of polymer-shelled bubbles with controlled dimensions generated from air-in-oil-in-water (A/O/W) compound bubbles. We show that the ratio of the shell thickness to bubble radius is critical in generating un-deformed polymer-shelled bubbles from A/O/W compound bubbles. In addition, the effects of shell stiffness and encapsulated gas on bubble stability are also investigated.

Micropipette aspiration of double emulsion-templated polymersomes

We measured the materials properties of polymersomes templated by double emulsions. Using micropipette aspiration, we verified the unilamellarity of fluid membranes consisting of PEO30-b-PBD46 diblock copolymers. In addition, we used micropipette aspiration to both track and verify solvent removal from double emulsion-templated polymersomes.

Brownian dynamics of colloidal probes during protein-layer formation at an oil–water interface

We employ the Brownian motion of spherical colloids to investigate the microrheology of layers of the protein β-lactoglobulin adsorbing at a decane–water interface. Using an experimental design in which the protein concentration in the aqueous subphase increases in a diffusion-limited manner, we obtain a time-resolved characterization of the interfacial rheology. After undergoing a period of increasing interfacial viscosity, the layers become viscoelastic with a rheology that indicates an approach to a sol–gel transition. This evolution, which depends on subphase pH, contrasts in several significant ways with layer formation by β-lactoglobulin at an air–water interface. Comparison of the diffusivity of colloids of two sizes as the interfacial viscosity increases illustrates the transformation in particle mobility from a three-dimensional character in which the surrounding bulk fluids dominate to a two-dimensional form dictated by the drag from the interfacial layer. This transformation is similarly revealed in the two-point correlations of the particle motion, which show a change in spatial dependence indicating a crossover from three-dimensional to two-dimensional hydrodynamics.

Interfacial hydrodynamic drag on nanowires embedded in thin oil films and protein layers.

We investigate the motion of ferromagnetic nanowires confined to nanometer-scale oil films at an air/aqueous interface in response to the application of external magnetic fields and field gradients. By varying the oil viscosity, film thickness, and wire length, we cover two regimes of response suggested by theory: one where the surface viscosity is expected to dominate the wires motion and one where the subphase viscosity is expected to dominate [Levine, A. J.; Liverpool, T. B.; MacKintosh, F. C. Phys. Rev. E 2004, 69, 021503]. For wire motion parallel to the long axis of the wire, the observed drag agrees reasonably with theoretical predictions. However, the drag on wires moving perpendicular to their long axis or rotating about a short axis is unexpectedly insensitive to the film properties over the full range of measurements. This behavior is in contrast to the rotational and translational drag on nanowires in molecularly thin protein layers, which follow theoretical expectations. The observations in the oil films, which are explained in terms of the manner in which the wire immerses dynamically in the film and subphase, demonstrate how the effective drag viscosity of an aspherical particle confined to a fluid interface can depend on its direction of motion.

Effect of composition on water permeability of model stratum corneum lipid membranes

The stratum corneum (SC), composed of corneocytes and intercellular lipid membranes, is the outermost layer of the epidermis, and its main function is the regulation of water loss from the skin. The major components of the SC lipid membranes are ceramides (CER), cholesterol (CHOL), and free fatty acids (FFA), which are organized in multilamellar structures between corneocytes. The intercellular SC lipid membrane is believed to provide the main pathway for the transport of water and other substances through the skin. While changes in the composition of the SC lipid membranes have been shown to affect the organization of the lipid molecules, little is known about the effect of compositional changes on their water permeability. In this work, we study the effect of membrane composition on the water permeability of model SC lipid membranes using a quartz crystal microbalance with dissipation monitoring (QCM-D). The QCM-D method enables the direct determination of the diffusivity (D), solubility (S), and permeability (P) of water through the model SC lipid membranes. We find that D and S weakly depend on the chain length of saturated fatty acids, while P shows no significant dependence. In contrast, the saturation level of free fatty acids and the structure of ceramide have significant influence on D and S, respectively, resulting in significant changes in P. By taking advantage of the dissipation monitoring capability of the QCM-D at multiple overtones, we find that the shear modulus (G) of the SC lipid membranes depends on its composition and decreases upon water absorption by the membranes.