Macromolecule-based
therapeutic agents, particularly proteins,
antigens, monoclonal antibodies, transcription factors, nucleic acids,
and gene editing enzymes, have the potential to offer cures for previously
untreatable diseases. However, they present an enormous delivery challenge
due to poor absorption and rapid metabolism in the body. Polymersomes
have tremendous potential in delivering these agents to their desired
intracellular location due to increased circulation times, decreased
macromolecule degradation, and decreased immune responses. In this
Review, we highlight the key factors in design, development, and improved
performance of these vesicles for macromolecular delivery. The recent
progress made toward preclinical application of these vesicles for
protein and gene delivery is also covered.
Surface charge plays an important role in determining the interactions of nanoparticles with biological components. Substantial studies have demonstrated that surface charge affects the fate of nanoparticles after intravenous administration; however, few studies have investigated the effect of surface charge on the bioavailability and absorption of nanoparticles after oral administration. In this study, polymeric nanoparticles with a similar particle size and surface polyethylene glycol (PEG) density, but with varying surface charges (positive, negative and neutral), were developed to study the effect of surface charge on the oral absorption of polymeric nanoparticles. The nanoparticles were constructed from polyethylene glycol-block-polylactic acid (PEG-PLA) with the incorporation of lipid components with different charges. Our results suggested that the positive surface charge facilitated the cellular uptake and transport of nanoparticles through both Caco-2 cells in vitro and small intestinal epithelial cells in vivo. The positively charged nanoparticles showed a favorable distribution in the small intestine, and significantly improved the oral bioavailability. This study presents valuable information towards the design of nanoparticles for improved oral drug delivery.
Miniaturized bioanalytical systems are increasingly being used in the field of biochemical research. Immobilized enzyme microbioreactors in capillary electrophoresis (CE) have been constructed and used to fulfill the increasing demands for miniaturized bioanalytical systems. This manipulation permits low sample consumption, reduced costs, short analysis times and efficient analyses. This review provides an overview of the distinct characteristics of immobilized microbioreactors in CE. After an introduction on miniaturized microreactors, the various methods of enzyme immobilization will be discussed. The emphasis will be on two common constructions of microreactors in CE, i.e. CE-coupled microreactors, and microreactors directly integrated into the CE capillary. Such microbioreactors offer straightforward automation of reaction steps followed by separation in the same capillary.
Nucleic acid‐based macromolecules have paved new avenues for the development of therapeutic interventions against a spectrum of diseases; however, their clinical translation is limited by successful delivery to the target site and cells. Therefore, numerous systems have been developed to overcome delivery challenges to nucleic acids. From the viewpoint of clinical translation, it is highly desirable to develop systems with clinically validated materials and controllability in synthesis. With this in mind, a cationic lipid assisted PEG‐b‐PLA nanoparticle (CLAN) is designed that is capable of protecting nucleic acids via encapsulation inside the aqueous core, and delivers them to target cells, while maintaining or improving nucleic acid function. The system is formulated from clinically validated components (PEG‐b‐PLA and its derivatives) and can be scaled‐up for large scale manufacturing, offering potential for its future use in clinical applications. Here, the development and working mechanisms of CLANs, the ways to improve its delivery efficacy, and its application in various disease treatments are summarized. Finally, a prospective for the further development of CLAN is also discussed.
When the clutch is in disengaged condition, ideally no torque should be transmitted. However, in reality, the relative motion between the disks causes viscous shearing of fluids in the gap. This results in a drag torque which is considered as a loss. The objective of the present study is to formulate a drag torque model as well as to experimentally evaluate the effect of several parameters on the drag torque. A model based on continuity and Navier-Stokes equations, considering laminar flow, is deduced. The drag torque estimated by the model is the sum of drag torque due to shearing of the automatic transmission fluid (ATF) and mist (suspension of ATF in air) film. In order to validate the model and characterize the drag torque, experiments are performed using an SAE no. 2 test setup under real conditions of variable ATF flow rate and disks' rotational states for higher clutch speed range. The drag torque predicted by the model is in good agreement with the experimental results obtained by varying the flow properties and disks' rotational states. By analyzing the experimental results, a factor by which, the variation in parameters such as ATF flow rate, ATF temperature, disk size, and disk rotational state influencing the drag torque is determined.
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