Microchamber arrays made of biodegradable polymers for enzymatic release of small hydrophilic cargos.

The encapsulation of small hydrophilic molecules and response to specific biological triggers in a controlled manner have become two of the significant challenges in biomedical research, in particular in the field of localized drug delivery and biosensing. This work reports the fabrication of free-standing microchamber array films made of biodegradable polymers for the encapsulation and enzymatically triggered release of small hydrophilic molecules. Polycaprolactone (PCL) microchamber arrays were demonstrated to fully biodegrade within 5 hours of exposure to lipase from Pseudomonas cepacia (lipase PS) at a concentration of 0.5 mg ml-1, with lower concentrations producing correspondingly longer degradation times. The gradual process of deterioration was real-time monitored utilising laser Fraunhofer diffraction patterns. Additionally, a small hydrophilic molecule, 5(6)-carboxyfluorescein (CF), was loaded into the PCL microchamber arrays in a dry state; however, the substantial permeability of the PCL film led to leakage of the dye molecules. Consequently, polylactic acid (PLA) was blended with PCL to reduce its permeability, enabling blended PCL-PLA (1 : 2 ratio correspondingly) microchamber arrays to trap the small hydrophilic molecule CF. PCL-PLA (1 : 2) microchamber arrays hold potential for controlled release under the catalysis of lipase within 26 hours. Additionally, it is calculated that approximately 11 pg of CF dye crystals was loaded into individual microchambers of 10 µm size, indicating that the microchamber array films could yield a highly efficient encapsulation.

Leucocyte Membrane-Coated Janus Microcapsules for Enhanced Photothermal Cancer Treatment.

Polyelectrolyte multilayer (PEM) capsules are promising candidates for many kinds of cancer detection and treatment but are usually intended to deliver cargo to specific sites or to destroy cancer cells based on photothermal effects from the outside. In this publication we prove that it is possible to kill cancer cells from the inside based on phagocytosed PEM capsules. In addition we show how to open the cells and bring the PEM capsules to the surface of cancer cells based on photothermal effects and rapid evaporation of water. Diffusion-based temperature determinations of the photothermal effect up to the evaporation temperature of water are presented.

Remote-Controllable Explosive Polymer Multilayer Tubes for Rapid Cancer Cell Killing.

Gold nanoshell-functionalized polymer multilayer tubes can be used as potent therapeutic agents for remote killing of cancer cells in a controlled manner due to the emerging pressure wave and tube fragments piercing the cell wall. The explosion is based on rapid evaporation of water inside the tubes caused by photothermal effects. The mechanism of explosion is presented in theory and experiment. The explosion of the tubes depends on the absorption coefficient and size of the gold nanoshells in the tubes, whereby the placement of the gold particles inside or outside of the tubes has no obvious effect on the explosive properties.

Influence of polyelectrolyte multilayer coating on the degree and type of biofouling in freshwater environment.

Biofouling is one of the biggest problems of water-borne systems. Since not only marine but also freshwater-based structures are affected, the biofouling in this environment is studied. The focus of this study lies on the antifouling properties of novel coating materials like polyelectrolyte multilayers (PEM) compared with currently used silicon rubber (PDMS) based fouling release coatings. The following article contains the results of a systematical screening of the mechanical, surface charge and surface nano-heterogeneous properties of the investigated PEM and PDMS systems. The results show that negatively charged non crosslinked and crosslinked PEM coated PDMS can surpass current PDMS based fouling release coatings. The PEM films are not only able to reduce the biofouling, but are additionally able to control the type of settled bacteria (gram positive or negative). The negative terminated surfaces inhibit the settlement of gram positive bacteria, whereby the positive terminated surfaces inhibit the settlement of gram negative bacteria.

Novel controllable auxetic effect of linearly elongated supported polyelectrolyte multilayers with amorphous structure.

Polyelectrolyte multilayers (PEMs) deposited on flexible supports are promising candidates for many applications ranging from controlled wettability over stimuli responsive nanovalves to lithography free surface structuring. Since many potential applications involve elongation of these films, we investigated the effect of elongation on the PEM thickness and density with ellipsometry. To our surprise PEM films with known amorphous internal structure show auxetic behavior that depends on the PEM preparation condition. The measured refractive index was compared with simulated values using the Garnet equation to evaluate if the incorporation of water or air causes the observed phenomena.

Biodegradable magnesium fuel-based Janus micromotors with surfactant induced motion direction reversal.

The speed and motion directionality of bubble-propelled micromotors is dependent on bubble lifetime, bubble formation frequency and bubble stabilization. Absence and presence of bubble stabilizing agents should significantly influence speed and propulsion pattern of a micromotor, especially for fast-diffusing molecules like hydrogen. This study demonstrates a fully biodegradable Janus structured micromotor, propelled by hydrogen bubbles generated by the chemical reaction between hydrochloric acid and magnesium. Six different concentrations of hydrochloric acid and five different concentrations of the surfactant Triton X-100 were tested, which also cover the critical micelle concentration at a pH corresponding to an empty stomach. The Janus micromotor reverses its propulsion direction depending on the availability and concentration of a surfactant. Upon surfactant-free condition, the Janus micromotor is propelled by bubble cavitation, causing the micromotor to be pulled at high speed for short time intervals into the direction of the imploding bubble and thus backwards. In case of available surfactant above the critical micelle concentration, the Janus micromotor is pushed forward by the generated bubbles, which emerge at high frequency and form a bubble trail. The finding of the propulsion direction reversal effect demonstrates the importance to investigate the motion properties of artificial micromotors in a variety of different environments prior to application, especially with surfactants, since biological media often contain large amounts of surface-active components.

pH dependent degradation properties of lactide based 3D microchamber arrays for sustained cargo release.

Encapsulation of small water soluble molecules is important in a large variety of applications, ranging from medical substance releasing implants in the field of medicine over release of catalytically active substances in the field of chemical processing to anti-corrosion agents in industry. In this work polylactic acid (PLA) based hollow-structured microchamber (MC) arrays are fabricated via one-step dip coating of a silicone rubber stamp into PLA solution. These PLA MCs are able to retain small water soluble molecules (Rhodamine B) stably entrapped within aqueous environments. It is shown, that degradation of PLA MCs strongly depends on environmental conditions like surrounding pH and follows first order degradation kinetics. This pH dependent PLA MC degradation can be utilized to control the release kinetics of encapsulated cargo.

Laser-triggered drug release from polymeric 3-D micro-structured films via optical fibers.

Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.

Polylactic acid sealed polyelectrolyte complex microcontainers for controlled encapsulation and NIR-Laser based release of cargo.

Surface mediated drug delivery is important for a large variety of applications, especially in medicine to control cell growth, prevent blood platelet activation on implants or for self-disinfecting devices (e.g. catheters). In industrial applications, controlled release of substances from surfaces is needed in a broad range of applications from anti-corrosion systems to anti-biofouling. Polyelectrolyte multilayers (PEM) based microcontainers (MCs) require several days production time, while MCs composed out of polylactic acid (PLA) are entirely hydrophobic, offering no functionality. We hereby present an approach to fabricate PLA coated synthetic as well as biopolymer based biodegradable polyelectrolyte complex MCs able to encapsulate small hydrophilic cargo within less than one hour. The chambers facilitate laser controlled release of cargo within submerged conditions.

In-situ NIR-laser mediated bioactive substance delivery to single cell for EGFP expression based on biocompatible microchamber-arrays.

Controlled drug delivery and gene expression is required for a large variety of applications including cancer therapy, wound healing, cell migration, cell modification, cell-analysis, reproductive and regenerative medicine. Controlled delivery of precise amounts of drugs to a single cell is especially interesting for cell and tissue engineering as well as therapeutics and has until now required the application of micro-pipettes, precisely placed dispersed drug delivery vehicles, or injections close to or into the cell. Here we present surface bound micro-chamber arrays able to store small hydrophilic molecules for prolonged times in subaqueous conditions supporting spatiotemporal near infrared laser mediated release. The micro-chambers (MCs) are composed of biocompatible and biodegradable polylactic acid (PLA). Biocompatible gold nanoparticles are employed as light harvesting agents to facilitate photothermal MC opening. The degree of photothermal heating is determined by numerical simulations utilizing optical properties of the MC, and confirmed by Brownian motion measurements of laser-irradiated micro-particles exhibiting similar optical properties like the MCs. The amount of bioactive small molecular cargo (doxycycline) from local release is determined by fluorescence spectroscopy and gene expression in isolated C2C12 cells via enhanced green fluorescent protein (EGFP) biosynthesis.

How Leucocyte Cell Membrane Modified Janus Microcapsules are Phagocytosed by Cancer Cells.

Modern drug delivery systems rely on either antibody-based single-surface recognition or on surface-hydrophobicity-based approaches. For a tumor showing various surface mutations, both approaches fail. This publication hereby presents Janus capsules based on polyelectrolyte multilayer microcapsules exhibiting human leucocyte (THP-1 cell line) cell membranes for discriminating HUVEC cells from three different cancer cell lines. Despite destroying the cellular integrity of leucocyte cells, the modified Janus capsules are able to adhere to cancer cells. Leucocyte cell-membrane-coated Janus capsules are phagocytosed with the cellular membrane part pointing to the cells.

Effect of linear elongation on carbon nanotube and polyelectrolyte structures in PDMS-supported nanocomposite LbL films.

Polyelectrolyte (PE) multilayer (PEM) thin films prepared by layer-by-layer self-assembly on flexible substrates are exposed to elongation in many fields of technology. Upon elongation, these types of films are showing interesting, but not understood, phenomena, such as controlled wetting, stimuli-responsive nanovalves, and lithography-free surface structuring. To investigate the mechanisms causing these interesting phenomena, we employed spectroscopic investigations of supported PEM films that were prepared from polystyrene sulfonate (PSS)-wrapped single-walled carbon nanotubes (SWNTs) or pyrene-labeled PSS (PSS-PY) and polydiallyldiammonium chloride. Our results show that the SWNTs agglomerated upon deposition into the PEM and showed a strong change in orientation upon uniaxial elongation of the PEM. Upon release of elongation, the resulting wrinkling pattern was changing its wavelength upon time, in the case of the SWNT-containing PEM. Fluorescence measurements of the PSS-PY in the PEM showed that the PEs changed their orientation due to constant mechanical force from elongation up to a time scale of 2 days after beginning the elongation. The results prove that elongated and released PEM films, until now considered static structures, possess strong kinetics, which has to be taken into account for their application.