Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs

For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself. However, it is unclear if the improved immunologic profiles can translate to better clinical outcomes since improved immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB nanocage (PCB NC) is developed, which can physically encase proteins while keeping their structure intact. PCB NC encapsulation of uricase, a highly immunogenic enzyme, is demonstrated to eradicate all the immune responses. To bridge the gap between immunogenicity and efficacy studies, the therapeutic performance of PCB NC uricase is evaluated and compared with its PEGylated counterpart in a clinical‐mimicking gouty rat model to determine any loss of efficacy evoked after five administrations.     

Self‐Healing Zwitterionic Microgels as a Versatile Platform for Malleable Cell Constructs and Injectable Therapies

Injectable and malleable hydrogels that combine excellent biocompatibility, physiological stability, and ease of use are highly desirable for biomedical applications. Here, a simple and scalable strategy is reported to make injectable and malleable zwitterionic polycarboxybetaine hydrogels, which are superhydrophilic, nonimmunogenic, and completely devoid of nonspecific interactions. When zwitterionic microgels are reconstructed, the combination of covalent crosslinking inside each microgel and supramolecular interactions between them gives the resulting zwitterionic injectable pellet (ZIP) constructs supportive moduli and tunable viscoelasticity. ZIP constructs can be lyophilized to a sterile powder that fully recovers its strength and elasticity upon rehydration, simplifying storage and formulation. The lyophilized powder can be reconstituted with any aqueous suspension of cells or therapeutics, and rapidly and spontaneously self‐heals into a homogeneous composite construct. This versatile and highly biocompatible platform material shows great promise for many applications, including as an injectable cell culture scaffold that promotes multipotent stem cell expansion and provides oxidative stress protection.     

Membrane functionalization using bisamide-based organic frameworks for molecular weight cutoff reduction

Functional polymers or copolymers have been added to separations membranes by incorporating them in the membrane dope prior to casting, by in situ polymerization, and by postsynthesis surface modification of existing membranes. Here, a postsynthesis membrane functionalization that targeted decreasing the molecular weight cutoff (MWCO) and increasing the hydrophilicity without significantly decreasing the operating flux was studied. Hybrid bisamide molecules with added amine and carboxylic acid functionalities as end groups were synthesized to form a selective layer on membrane surface via covalent attachment to the membrane. Fourier transform infrared spectroscopy analysis showed the functional groups corresponding to bisamide molecules were present on modified membranes. Furthermore, modified membranes displayed MWCO of 400 Da as compared to 1000 Da MWCO of unmodified membranes, along with an increase in the hydrophilicity of modified membranes. Modified membranes showed an improvement in divalent salt rejection and percent flux recovered after reverse-flow filtration as compared to unmodified membranes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48327.     

Discovering 3D Surface Information Values from Gameplayers

A novel algorithm discovers surface information values from collected player data. Designers can use this information to place artifacts so as to improve or obscure observation, as intended. In a validation user study that implemented this approach, players viewed 84 percent of artifacts placed in high-value information locations.     

Erratum to: Effect of interface on mid-infrared photothermal response of MoS2 thin film grown by pulsed laser deposition

Nano Research - The correspondence author in the original version of this article was unfortunately wrongly written on page 3571 and the first page of the ESM. Instead of Ankur Goswami1, Priyesh...     

A Coating‐Free Nonfouling Polymeric Elastomer

Medical devices face nonspecific biofouling from proteins, cells, and microorganisms, which significantly contributes to complications and device failure. Imparting these devices with nonfouling capabilities remains a major challenge, particularly for those made from elastomeric polymers. Current strategies, including surface coating and copolymerization/physical blending, necessitate compromise among nonfouling properties, durability, and mechanical strength. Here, a new strategy is reported to achieve both high bulk mechanical strength and excellent surface nonfouling properties, which are typically contradictory, in one material. This is realized through a nonfouling polymeric elastomer based on zwitterionic polycarboxybetaine derivatives. By hiding both charged moieties of the zwitterionic compounds with hydrocarbon ester and tertiary amine groups, the bulk polymer itself is elastomeric and hydrophobic while its superhydrophilic surface properties are restored upon hydrolysis. This coating‐free nonfouling elastomer is a highly promising biomaterial for biomedical and engineering applications.     

Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery

Context: Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs.

Objective: The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated.

Materials and methods: Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr’s index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose^® (SV003, Goch, Germany)] used in DPI formulations.

Results and discussion: EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose^® (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose^® (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology.

Conclusion: Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.