Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Missing perilymph but leaking blood-endolymph and vestibulocochlear nerve barriers in idiopathic sudden sensorineural hearing loss:A case study

Objectives:To evaluate the pathological changes in the blood-perilymph,blood-endolymph,and bloodnerve barriers of a patient with idiopathic sudden sensorineural hearing loss(SSNHL).Methods:Potential ossification or fibrosis in the inner ear was evaluated using temporal bone CT and MRI acquired using the 3-dimensional T2-weighted sampling perfection with application-optimized contrasts using a flip angle evolution sequence.Pathological changes in the barriers were analyzed by MRI obtained 4 h after a single-dose intravenous injection of gadolinium chelate using a medium inversiontime inversion recovery imaging with magnitude reconstruction sequence.Results:The perilymph was absent,while significant enhancements of the vestibulocochlear nerve and the endolymphatic compartments were detected.Conclusion:Significant injuries in the blood-endolymph and blood-vestibulocochlear nerve barriers and disabled perilymph production may contribute to the development of SSNHL with poor response to treatments.

Woodchip-sulfur packed biological permeable reactive barrier for mixotrophic vanadium(V)detoxification in groundwater

Groundwater vanadium(V)(V(V))contamination is ubiquitous in vanadium mining/smelting region and development of novel strategy for its remediation is of particular significance.Herein woodchip-sulfur packed biological permeable reactive barrier(bio-PRB)is established towards successful V(V)bio-detoxification.V(V)removal was accelerated under such mixotrophic condition,compared with heterotrophic and autotrophic V(V)reductions.The performance of bio-PRB was relatively steady with V(V)removal efficiency of 68.5%–98.2%under fluctuant geochemical and hydrodynamic conditions.Microbial community analysis indicated that heterotrophic Geobacter was the main reducer to convert V(V)to insoluble V(IV),by consumption of organic source attributed to woodchip hydrolysis and sulfur anabolism of autotrophs(e.g.,Sulfuricurvum and Thiobacillus).V(V)reduction and elemental sulfur oxidation were regulated by genes as omcA,omcB and mtrC and soxB,respectively.The elevated contents of cytochrome c and nicotinamide adenine dinucleotide implied that improved electron transfer facilitated V(V)reduction.This study provides a cost-effective,robust and sustainable route for V(V)-polluted aquifer remediation.

Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives

Diabetes,characterized by hyperglycemia,is a major cause of death and disability worldwide.Peptides,such as insulin and glucagon-like peptide-1(GLP-1)analogs,have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the body.Compared to subcutaneous injection,oral administration of anti-diabetic peptides is a preferred approach.However,biological barriers significantly reduce the efficacy of oral peptide therapeutics.Recent advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating diabetes.This review will highlight(1)the benefits of oral anti-diabetic peptide therapeutics;(2)the biological barriers for oral peptide delivery,including pH and enzyme degradation,intestinal mucosa barrier,and biodistribution barrier;(3)the delivery platforms to overcome these biological barriers.Additionally,the review will discuss the prospects in this field.The information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.

Nano-bio interactions: the implication of size-dependent biological effects of nanomaterials

Due to their many advantageous properties,nanomaterials(NMs)have been utilized in diverse consumer goods,industrial products,and for therapeutic purposes.This situation leads to a constant risk of exposure and uptake by the human body,which are highly dependent on nanomaterial size.Consequently,an improved understanding of the interactions between different sizes of nanomaterials and biological systems is needed to design safer and more clinically relevant nano systems.We discuss the sizedependent effects of nanomaterials in living organisms.Upon entry into biological systems,nanomaterials can translocate biological barriers,distribute to various tissues and elicit different toxic effects on organs,based on their size and location.The association of nanomaterial size with physiological structures within organs determines the site of accumulation of nanoparticles.In general,nanomaterials smaller than 20 nm tend to accumulate in the kidney while nanomaterials between 20 and 100 nm preferentially deposit in the liver.After accumulating in organs,nanomaterials can induce inflammation,damage structural integrity and ultimately result in organ dysfunction,which helps better understand the size-dependent dynamic processes and toxicity of nanomaterials in organisms.The enhanced permeability and retention effect of nanomaterials and the utility of this phenomenon in tumor therapy are also highlighted.

The feasibility of oral targeted drug delivery: Gut immune to particulates?

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration(oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.

Medical micro-and nanomotors in the body

Attributed to the miniaturized body size and active mobility,micro-and nanomotors(MNMs)have demonstrated tremendous potential for medical applications.However,from bench to bedside,massive efforts are needed to address critical issues,such as cost-effective fabrication,on-demand integration of multiple functions,biocompatibility,biodegradability,controlled propulsion and in vivo navigation.Herein,we summarize the advances of biomedical MNMs reported in the past two decades,with particular emphasis on the design,fabrication,propulsion,navigation,and the abilities of biological barriers penetration,biosensing,diagnosis,minimally invasive surgery and targeted cargo delivery.Future perspectives and challenges are discussed as well.This review can lay the foundation for the future direction of medical MNMs,pushing one step forward on the road to achieving practical theranostics using MNMs.

Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery

High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient cells.Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.

Loss of soil microbial diversity exacerbates spread of antibiotic resistance

Loss of biodiversity is a major threat to the ecosystem processes upon which society depends.Natural ecosystems differ in their resistance to invasion by alien species,and this resistance can depend on the diversity in the system.Little is known,however,about the barriers that microbial diversity provides against microbial invasion.The increasing prevalence of antibioticresistant bacteria is a serious threat to public health in the 21st century.We explored the consequences of the reduction in soil microbial diversity for the dissemination of antibiotic resistance.The relationship between this diversity and the invasion of antibiotic resistance was investigated using a dilution-to-extinction approach coupled with high-capacity quantitative PCR.Microbial diversity was negatively correlated with the abundance of antibiotic-resistance genes,and this correlation was maintained after accounting for other potential drivers such as incubation time and microbial abundance.Our results demonstrate that high microbial diversity can act as a biological barrier resist the spread of antibiotic resistance.These results fill a critical gap in our understanding of the role of soil microbial diversity in the health of ecosystems.