Throughout the past decade, zwitterionic moieties have gained attention as constituents of biocompatible materials for exhibiting superhydrophilic properties that prevent nonspecific protein adsorption. Researchers have been working to synthesize zwitterionic materials for diverse biomedical applications such as drug delivery, protein stabilization, and surface modification of implantable materials. These zwitterionic materials have been used in assorted architectures, including protein conjugates, surface coatings, nanoparticles, hydrogels, and liposomes. Herein, we summarize recent advancements that further our understanding of interactions between biomolecules and zwitterionic moieties. We focus on the solution behavior of zwitterions and zwitterionic polymers and the molecular interactions between these molecules and biomolecules as determined by both experimental and theoretical studies. Further, we discuss the implications of using such interactions in vivo and how zwitterionic moieties may be incorporated to facilitate targeted delivery of proteins, genes, or small molecules. Finally, we discuss current knowledge gaps that need to be addressed to advance the field.
Inorganic/organic
hybrid nanosystems have been increasingly developed
for their versatility and efficacy at overcoming obstacles not readily
surmounted by nonhybridized counterparts. Currently, hybrid nanosystems
are implemented for gene therapy, drug delivery, and phototherapy
in addition to tissue regeneration, vaccines, antibacterials, biomolecule
detection, imaging probes, and theranostics. Though diverse, these
nanosystems can be classified according to foundational inorganic/organic
components, accessory moieties, and architecture of hybridization.
Within this Review, we begin by providing a historical context for
the development of biomedical hybrid nanosystems before describing
the properties, synthesis, and characterization of their component
building blocks. Afterward, we introduce the architectures of hybridization
and highlight recent biomedical nanosystem developments by area of
application, emphasizing hybrids of distinctive utility and innovation.
Finally, we draw attention to ongoing clinical trials before recapping
our discussion of hybrid nanosystems and providing a perspective on
the future of the field.
Therapeutic proteins are utilized in a variety of clinical applications, but side effects and rapid in vivo clearance still present hurdles. An approach that addresses both drawbacks is protein encapsulation within in a polymeric nanoparticle, which is effective but introduces the additional challenge of destabilizing the nanoparticle shell in clinically-relevant locations. This study examined the effects of crosslinking self-This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
There is emerging evidence that biocompatible zwitterionic materials can prevent nonspecific interactions within protein systems and increase protein stability. Here, a zwitterionic microgel was synthesized from poly (carboxybetaine methyl methacrylate) (pCB) using an inverse emulsion, free radical polymerization reaction technique. The microgel was loaded with a model enzyme, α‐chymotrypsin (ChT), using a post‐fabrication loading technique. A reaction scheme was developed and studied for covalent immobilization of ChT within the microgel. Confocal laser microscopy studies showed that immobilized ChT (i‐ChT) was distributed within the hydrogel. The enzyme‐immobilized microgels showed excellent reusability (72% of its initial activity after 10 uses) and could undergo several freezing/drying/rehydration cycles while retaining enzymatic activity. The i‐ChT activity, half‐life, and conformational stability were studied at varying pH and temperatures with results compared to free ChT in buffer. ChT immobilized within pCB hydrogel showed increased enzymatic stability as observed by a 13°C increase in the temperature at which i‐ChT loses activity compared to free ChT. Furthermore, enzyme half‐life increased up to seven‐fold for the pCB immobilized ChT, and the increased stability resulted in higher activity at elevated pH. The i‐ChT was most active at pH of 8.5 and was partially active up to the pH of 10.2.
There is emerging evidence showing how biocompatible zwitterionic materials can prevent non‐specific interactions within protein systems, increasing protein stability. In this cover designed by Clint P. Aichele and collagues, a zwitterionic microgel was synthesized from poly (carboxybetaine methyl methacrylate) (pCB) using an inverse emulsion, a free radical polymerization reaction technique. The microgel was loaded with a model enzyme, α‐chymotrypsin (ChT), using a post‐fabrication loading technique. A reaction scheme was developed and studied for covalent immobilization of ChT within the microgel. The enzyme‐immobilized microgels showed excellent reusability and increased enzymatic stability. Furthermore, enzyme half‐life increased up to seven‐fold for the pCB immobilized ChT, and the increased stability resulted in higher activity at elevated pH. Doi: https://doi.org/10.1002/app.50545
Point of Use (POU) drinking water treatment shows potential to save the lives of thousands who die every day from preventable waterborne illnesses. Most POU treatment focuses on either household scale filtration or community-level disinfection, but there remains a need for a low-cost batch treatment system incorporating both filtration and disinfection. Consequently, a drinking water treatment system including sand filtration and locally-generated chemical disinfection was constructed from inexpensive and accessible materials. The prototype consisted of two barrels and a circulation pump, with water cycling through a gravity sand filter before being injected with chlorine produced through saline electrolysis. The treatment efficacy of the prototype was determined by turbidity reduction and disinfection effectiveness. Ninety gallons of surface water displayed a 70% reduction in turbidity after ninety minutes of operation, and no coliform bacteria were detected in the system upon completion of treatment. The purchase cost of the system components was less than $900 (2017) and the total project displays an estimated net present value of ($4,100) over 10 years. The system is safe, simple, and reliable, and could be foundational to the development and implementation of chemical disinfection in batch filtration processes for POU water treatment.
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