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In drug delivery, enzyme-responsive drug carriers are becoming increasingly relevant because of the growing association of disease pathology with enzyme overexpression. Polymersomes are of interest to such applications because of their tunable properties. While polymersomes open up a wide range of chemical and physical properties to explore, they also present a challenge in developing generalized rules for the synthesis of novel systems. Motivated by this issue, in this perspective, we summarize the existing knowledge on enzyme-responsive polymersomes and outline the main design choices. Then, we propose heuristics to guide the design of novel systems. Finally, we discuss the potential of an integrated approach using computer simulations and experimental studies to streamline this design process and close the existing knowledge gaps.

Polyethylene glycol-b-polylactic acid (PEGPLA) polymersomes elongate under osmotic pressure. Hypertonic NaCl solutions statistically increased the zeta potential from negative to neutral. Change in charge and PLA hydrophilicity allow for binding of polymersomes depots to increase membrane surface area. PEGPLA polymersomes exhibit biomimicry in their homeostatic responses to increased osmotic pressure.

Genetic diseases present formidable hurdles in maintaining a good quality of life for those suffering from these ailments. Often, patients look to inadequate treatments to manage symptoms, which can result in harmful effects on the body. Through genetic engineering, scientists utilize the clustered regularly short palindromic repeat (CRISPR)-associated protein, known as Cas9, to treat the root of the problem. The Cas9 protein is often codelivered with guide RNAs or in ribonucleoprotein complexes (RNP) to ensure targeted delivery of the genetic tool as well as to limit off-target effects. This paper provides an overview of the current advances made toward the encapsulation and delivery of Cas9 to desired locations in the body through encapsulating nanoparticles. Several factors must be considered when employing the Cas9 system to allow gene editing to occur. Material selection is crucial to protect the payload of the delivery vector. Current literature indicates that lipid- and polymer-based nanoparticles show the most potential as delivery vessels for Cas9. Lipid nanoparticles greatly outpace polymer-based nanoparticles in the clinic, despite the benefits that polymers may introduce. When developing translatable systems, there are factors that have not yet been considered that are relevant to Cas9 delivery that are highlighted in this Viewpoint. The proper functioning of Cas9 is dependent on maintaining a proper internal environment; however, there are gaps in the literature regarding these optimal conditions. Interactions between charges of the Cas9 protein, codelivered molecules, and delivery vehicles could impact the effectiveness of the gene editing taking place. While the internal charges of nanoparticles and their effects on Cas9 are presently undetermined, nanoparticles currently offer the ideal delivery method for the Cas9 protein due to their adequate size, modifiable external charge, and ability to be modified. Overall, a cationic lipid-/polymer-based nanoparticle system was found to have the most prospects in Cas9 delivery thus far. By understanding the successes of other systems, translatable, polymer-based delivery vehicles may be developed.

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.

Nanomedicine and targeted drug delivery systems hold significant promise, but suffer from a lack of successful translation into clinical use. A major factor is the inability to properly characterize important aspects of drug delivery systems in a realistic environment in vitro. Self-assembled particles are of particular concern because aqueous solutions may have different forces contributing to assembly, compared to the complex fluids inside the body. Characterization techniques for nanoparticles, the theory behind the techniques, and their shortcomings for use with blood are surveyed. Previous attempts to replicate or model blood for use with these techniques are examined. The complexity of blood, both its non-Newtonian nature and highly polydisperse cell and protein populations, makes it difficult to reliably study in situ nanoparticle properties in a way that resembles in vivo behavior. However, comparatively little focus is given to this issue: studies frequently use unreliable models of whole blood or jump from aqueous solutions directly to animal models, which can limit translational success. New technologies and methods to study nanoparticles in blood could provide valuable insight into how delivery systems will function in practice, and help to find promising candidates to move into animal or clinical trials.

How, as a sub-set of maritime security, can piracy studies contribute with conceptual insights of relevance to the field of international security governance and international politics more broadly? To answer this question the article examines, with reference to critical intervention studies, how responses to Somali piracy have had constitutive effects, notably ‘back onto’ the intervening actors themselves. More specifically, three themes are examined: regulation (law), structures (institutions) and practices (actors), each of which highlights a distinct sense of contingency, which both characterizes contemporary security governance at sea and makes ‘the maritime’ an interesting domain for the study of constitutive effects related to the making of intervention actors. In light of this, the article argues that studying ‘the maritime’ can offer conceptual insights to the constitutive effects of counter-piracy interventions that may prove relevant to broader debates about governance and security in a changing world order.

Polymersomes are membrane-bound, bilayer vesicles created from amphiphilic block copolymers that can encapsulate both hydrophobic and hydrophilic payloads for drug delivery applications. Despite their promise, polymersomes are limited in application due to their spherical shape, which is not readily taken up by cells, as demonstrated by solid nanoparticle scientists. This article describes a salt-based method for increasing the aspect ratios of spherical poly(ethylene glycol) (PEG)- based polymersomes. This method can elongate polymersomes and ultimately control their final shape by adding sodium chloride in post-formation dialysis. Salt concentration can be varied, as described in this method, based on the hydrophobicity of the block copolymer being used as the base for the polymersome and the target shape. Elongated nanoparticles have the potential to better target the endothelium in larger diameter blood vessels, like veins, where margination is observed. This protocol can expand therapeutic nanoparticle applications by utilizing elongation techniques in tandem with the dual-loading, long-circulating benefits of polymersomes.

This paper highlights the potential benefits of using self-assembled polymeric nanoparticles of various shapes to enhance drug uptake. First, we highlight the growth and development of the polymersome, using a liposome as a blueprint for amphiphilic codelivery. Then, we focus on the advantages of nanoparticle elongation, drawing from the field of solid nanoparticles, as opposed to self-assembled vesicles which have not yet been extensively explored in shape-modulated drug delivery applications. Notably, regardless of the material used in the solid nanoparticle systems, more elongated shapes lead to greater cellular uptake, decreased interaction with the reticuloendothelial system macrophages, and increased circulation times. Finally, we highlight the methods currently being developed to modulate polymersome shape, thus providing a drug delivery system with the benefits derived from amphiphilicity and elongated structures. Current methods employed to modulate polymersome shape involve osmotic pressure gradients, solvent switching, and the use of cross-linking agents. Although these methods are successful in modulating polymersome shapes and the benefits of elongated nanoparticles in therapeutic targeting are clear, these methods have not yet been explored for applications in drug delivery.

Background Although not routinely assessed, prenatal posttraumatic stress disorder (PTSD) is associated with poor maternal mental health and mother-infant bonding. Prenatal PTSD may also be associated with birth weight and gestational age outcomes, but this remains unclear. This systematic review and meta-analysis investigated the association of prenatal PTSD with risk of low birth weight (LBW) or preterm birth (PTB) (dichotomous medically-defined cut-offs) or with birth weight (BW) or gestational age (GA) (continuous variables). Methods A comprehensive literature search was conducted in Web of Science, MedLine, PubMed, and PsychInfo. Data were collected and processed according to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Study quality was assessed with the Newcastle-Ottowa Quality Assessment Scale. Pooled effect sizes were estimated with random-effects models (correlation for continuous and odds ratios for dichotomous outcomes). Results Sixteen studies with 51,470 participants (prenatal PTSD 8%) were included in 4 meta-analyses. Maternal prenatal PTSD was associated with higher risks of LBW (OR = 1.96; 95% CI, 1.26, 3.03; P = .003), PTB (OR = 1.42; 95% CI, 1.16, 1.73; P = .001), and reduced GA (r = -0.04; 95% CI, -0.06, -0.01; P = .002). Limitations Different designs across studies, variety of PTSD assessment practices, and a small pool of studies were noted. Conclusions Findings suggest prenatal PTSD presents increased risks of LBW, PTB, and reduced GA. Evidence of physical harm to neonates from prenatal PTSD provides a powerful rationale to increase prenatal PTSD screening and identify effective prenatal interventions to improve maternal and child outcomes.

Polyethylene glycol-b-polylactic acid (PEG–PLA) and polyethylene glycol-b-poly(lactic-co-glycolic) acid) (PEG–PLGA) are two copolymers made up of three currently FDA approved polymers, used as drug...

With an increasing aging population, neurodegenerative diseases are having an increased impact on society. Typically, these diseases are diagnosed significantly past symptom onset, decreasing the possibility of effective treatment. A non-invasive biomarker and specific target are needed to diagnose and treat the disease before late-stage symptoms. GM1 Gangliosidosis is a lysosomal storage disease where lysosomal enzyme β-galactosidase is missing. As a result, GM1 ganglioside is not broken down and accumulates in the cell, ultimately leading to cell death. One of the main aspects of GM1 Gangliosidosis, and other neurodegenerative diseases, is impaired autophagy: reduced fusion of autophagosomes and lysosomes to degrade cellular waste.In this paper, we show that healthy cells (NSV3) have approximately 13 times more co-localization of lysosomes and autophagosomes than GM1 Gangliosidosis-diseased cells (GM1SV3), as demonstrated via immunofluorescence. GM1SV3 fold normal enzyme activity of β-galactosidase was downregulated while mannosidase, and hexosaminidase A were both upregulated. When inducing impaired autophagy in NSV3 via starvation, co-localization gradually decreases with increased starvation time. Most notably, after 48-hour starvation, healthy cells (NSV3) showed no significant difference in co-localization compared to GM1SV3. NSV3 under starvation conditions showed a significant increase between time starved and fold normal enzyme activity, with a positive correlation being observed. Activities of mannosidase, and hexosaminidase A of starved NSV3 closely resemble, and surpass, GM1SV3 after 12-hour starvation.These observations have the potential to expand the conversation regarding impaired autophagy as a potential biomarker for disease progression and diagnostics and as a treatment target.

Self-assembled polymersomes encapsulate, protect, and deliver hydrophobic and hydrophilic drugs. Though spherical polymersomes are effective, early studies suggest that non-spherical structures may enhance specificity of delivery and uptake due to similarity to endogenous uptake targets. Here we describe a method to obtain persistent non-spherical shapes, prolates, via osmotic pressure and the effect of prolates on uptake behavior. Polyethylene glycol-b-poly(lactic acid) polymersomes change in diameter from 175 ± 5nm to 200 ± 5nm and increase in polydispersity from 0.06 ± 0.02 to 0.122 ± 0.01 nm after addition of 50 mM salt. Transmission and scanning electron microscopy confirm changes from spheres to prolates. Prolate-like polymersomes maintain their shape in 50 mM NaCl for seven days. Nile Red and bovine serum albumin(BSA)-Fluorescein dyes are taken up in greater amounts by SH-SY5Y neural cells when encapsulated in polymersomes. Prolate polymersomes may be taken up more efficiently in neural cells than spherical polymersomes.

Functional behavioral assessment (FBA) is an assessment strategy which focuses on identifying situational/environmental conditions associated with problem behaviors. The desired outcome of FBA is to understand the meaning (or function) of specific behaviors and eventually manipulate behavior–environment relationships across or within those conditions and promote more appropriate behaviors (Crone & Horner, 2003). While FBA has been widely researched and promoted for developmentally delayed and low incidence conditions, empirical support for these procedures with children with mild to moderate level disabilities remains a topic of some debate. Currently, an active discussion is occurring in research and clinical communities to determine whether the evidence available in both regular and special education school contexts is sufficient to warrant wholesale adoption of FBA in school settings, despite the conceptual soundness, legal support, and emerging evidence for the procedures in the literature (Crone & Horner, 2003; DuPaul, Eckert & McGoey, 1997; Ervin et al., 2001; Gresham, McIntyre, & Olson–Tinker, 2004).

The use of enzymatically isolated cardiac myocytes is ubiquitous in modern cardiovascular research. Parallels established between cardiomyocyte shortening responses and those of intact tissue make the cardiomyocyte an invaluable experimental model of cardiac function. Much of our understanding regarding the fundamental processes underlying heart function is owed to our increasing capabilities in single-cell stimulation and direct or indirect observation, as well as quantitative analysis of such cells. Of the many important mechanisms and functions that can be readily assessed in cardiomyocytes at all stages of development, contractility is the most representative and one of the most revealing. The purpose of this review is to provide a survey of various methodological approaches in the literature used to assess adult and neonatal cardiomyocyte contractility. The various methods employed to evaluate the contractile behavior of enzymatically isolated mammalian cardiac myocytes can be conveniently divided into two general categories—those employing optical (image)-based systems and those that use transducer-based technologies. This survey is by no means complete, but we have made an effort to include the most popular methods in terms of reliability and accessibility. These techniques are in constant evolution and hold great promise for the next generation of breakthrough studies in cell biology for the prevention, treatment, and cure of cardiovascular diseases.