Membrane folding and shape transformation in biomimetic vesicles.

Polymeric self-assembled structures have been a topic of interest in the last few decades, specifically for the use of biomedical applications, such as drug delivery. It is exciting to investigate the formation of various shapes and sizes of such structures, as the morphology is crucial for their function. In this manuscript the important factors to control the morphology during self-assembly and subsequent shape transformation processes are discussed. We describe the main parameters to control and show the practical application of these parameters on biodegradable amphiphilic PEG-PDLLA block-copolymers. Thereby a variety of different morphologies, including micelles, worms, LCVs, discs, rods, stomatocytes, nested vesicles, and spherical vesicles of various sizes are created using only four diblock-copolymers and with careful tuning of two organic solvents. Further advances will lead to formation of more complex structures.

Self-Propelled PLGA Micromotor with Chemotactic Response to Inflammation.

Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site-specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug-loaded biodegradable micromotors showing self-propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters-stimulated macrophages are reported. The drug-loaded poly(lactic-co-glycolic acid) micromotors with asymmetric coverage of enzyme (patch-like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high-performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters-stimulated macrophages.

Modular Approach to the Functionalization of Polymersomes.

Functionalizing polymersomes remains a challenge due to the limitation in reaction conditions applicable to the chemistry on the surface, hindering their application for selective targeting. In order to overcome this limitation, functionalization can be introduced right before the self-assembly. Here, we have synthesized a library (32 examples) of PEG-b-PS and PEG-b-PDLLA with various functional groups derived from the amine-functionalized polymers, leading to functionally active polymersomes. We show that polymersome formation is possible via the general method with all functionalized groups and that these handles are present on the surface and are able to undergo reactions. Additionally, this methodology provides a general synthetic tool to tailor the functional group of the polymersome right before self-assembly, without limitation on the reaction conditions.

Spatial control over catalyst positioning on biodegradable polymeric nanomotors.

Scientists over the world are inspired by biological nanomotors and try to mimic these complex structures. In recent years multiple nanomotors have been created for various fields, such as biomedical applications or environmental remediation, which require a different design both in terms of size and shape, as well as material properties. So far, only relatively simple designs for synthetic nanomotors have been reported. Herein, we report an approach to create biodegradable polymeric nanomotors with a multivalent design. PEG-PDLLA (poly(ethylene glycol)-b-poly(D,L-lactide)) stomatocytes with azide handles were created that were selectively reduced on the outside surface by TCEP (tris(2-carboxyethyl)phosphine) functionalized beads. Thereby, two different functional handles were created, both on the inner and outer surface of the stomatocytes, providing spatial control for catalyst positioning. Enzymes were coupled on the inside of the stomatocyte to induce motion in the presence of fuel, while fluorophores and other molecules can be attached on the outside.

Screening Libraries of Amphiphilic Janus Dendrimers Based on Natural Phenolic Acids to Discover Monodisperse Unilamellar Dendrimersomes.

Natural, including plant, and synthetic phenolic acids are employed as building blocks for the synthesis of constitutional isomeric libraries of self-assembling dendrons and dendrimers that are the simplest examples of programmed synthetic macromolecules. Amphiphilic Janus dendrimers are synthesized from a diversity of building blocks including natural phenolic acids. They self-assemble in water or buffer into vesicular dendrimersomes employed as biological membrane mimics, hybrid and synthetic cells. These dendrimersomes are predominantly uni- or multilamellar vesicles with size and polydispersity that is predicted by their primary structure. However, in numerous cases, unilamellar dendrimersomes completely free of multilamellar assemblies are desirable. Here, we report the synthesis and structural analysis of a library containing 13 amphiphilic Janus dendrimers containing linear and branched alkyl chains on their hydrophobic part. They were prepared by an optimized iterative modular synthesis starting from natural phenolic acids. Monodisperse dendrimersomes were prepared by injection and giant polydisperse by hydration. Both were structurally characterized to select the molecular design principles that provide unilamellar dendrimersomes in higher yields and shorter reaction times than under previously used reaction conditions. These dendrimersomes are expected to provide important tools for synthetic cell biology, encapsulation, and delivery.

Active, Autonomous, and Adaptive Polymeric Particles for Biomedical Applications.

Nature's motors are complex and efficient systems, which are able to respond to many different stimuli present in the cell. Nanomotors for biomedical applications are designed to mimic nature's complexity; however, they usually lack biocompatibility and the ability to adapt to their environment. Polymeric vesicles can overcome these problems due to the soft and flexible nature of polymers. Herein we will highlight the recent progress and the crucial steps needed to fabricate active and adaptive motor systems for their use in biomedical applications and our approach to reach this goal. This includes the formation of active, asymmetric vesicles and the incorporation of a catalyst, together with their potential in biological applications and the challenges still to overcome.

Clinical Evidence for Use of a Noninvasive Biosensor for Tear Glucose as an Alternative to Painful Finger-Prick for Diabetes Management Utilizing a Biopolymer Coating.

Diabetes is a metabolic condition that is exponentially increasing worldwide. Current monitoring methods for diabetes are invasive, painful, and expensive. Herein, we present the first multipatient clinical trial that demonstrates clearly that tear fluid may be a valuable marker for systemic glucose measurements. The NovioSense Glucose Sensor, worn under the lower eye lid (inferior conjunctival fornix), is reported to continuously measure glucose levels in the basal tear fluid with good correlation to blood glucose values, showing clear clinical feasibility in both animals and humans. Furthermore, the polysaccharide coated device previously reported by our laboratory when worn, does not induce pain or irritation. In a phase II clinical trial, six patients with type 1 Diabetes Mellitus were enrolled and the capability of the device to measure glucose in the tear fluid was evaluated. The NovioSense Glucose Sensor gives a stable signal and the results correlate well to blood glucose values obtained from finger-prick measurements determined by consensus error grid analysis.