Utilization of solid nanomaterials for drug delivery

Background: Solid nanostructures are versatile platforms for constructing hybrid drug delivery systems that have tremendous potential for improving disease prevention and treatment. The rationale and application of solid nanostructures in the context of drug delivery are explored in this article. Objective: The purpose of this paper is to provide a concise review of the major attributes of solid nanostructures as they relate to drug delivery and to describe the outstanding issues that need to be addressed in order to develop these materials into clinically useful reagents. Methods: The scope of this opinion has been restricted to solid nanostructures, where solid nanostructures are defined as those that are not biodegradable. The opinion has been further limited to the three primary types of nanostructures: nanoparticles, nanowires and nanotubes. Results/conclusion: There is a need for cross-disciplinary training and standardized protocols for developing and evaluating the efficacy of solid nanomaterials.     

Polymeric nano- and microparticle technologies for oral gene delivery

Gene therapy refers to local or systemic administration of a nucleic acid construct that can prevent, treat and even cure diseases by changing the expression of genes that are responsible for the pathological condition. Oral gene therapy has significant promise for treatment of local diseases such as inflammatory bowel disease and for systemic absorption of the expressed protein therapeutics. In addition, efficient oral delivery of DNA vaccines can have significant impact in disease prevention. The use of polymeric gene delivery vectors promises the translation of this experimental medical concept into clinical reality. This review addresses the challenges and opportunities in the development of polymer-based nano- and microparticle technologies for oral gene therapy. Specifically, the discussion is focused on different synthetic and natural polymers used for formulating nano- and microparticle technologies and the use of these delivery systems for oral DNA administration for therapeutic and vaccination purposes.     

Metabolomic method to detect a metabolite corona on amino-functionalized polystyrene nanoparticles

Abstract

Protein coronas on nanoparticles (NPs) affect their physicochemical properties, cellular uptake, and toxicity, and have been described extensively. To date, studies of the occurrence of small molecule (metabolite) coronas are limited. We sought to determine whether a metabolite corona forms on NPs, using high-sensitivity metabolomics combined with a model system for freshwater ecotoxicology (Daphnia magna feeding on Chlorella vulgaris). Using amino-functionalized polystyrene NPs (NH₂-pNPs), we showed the impact of this material on Daphnia feeding to provide a rationale for the detailed molecular investigations. We then employed a targeted LC-MS/MS approach for sodium dodecyl sulfate (SDS) as an analog to signaling molecules known to occur in our freshwater model system and optimized a corona extraction method for this representative metabolite. Next, we performed an untargeted discovery-based metabolomics study – using high-sensitivity nanoelectrospray direct infusion mass spectrometry (DIMS) – to enable an unbiased assessment of the metabolite corona of NH₂-pNPs in the freshwater model system. Our results demonstrate that SDS was successfully recovered from NH₂-pNPs, confirming that the extraction protocol was fit-for-purpose. Untargeted DIMS metabolomics reproducibly detected 100?s of small molecule peaks extracted from NH₂-pNPs exposed to conditioned media from the D. magna–C. vulgaris model system. Attempts to annotate these extracted metabolites, including by using van Krevelen and Kendrick Mass Defect plots, indicate a diverse range of metabolites that were not clustered into any particular class. Overall we demonstrate the existence of an ecologically relevant metabolite corona on the surface of NPs through application of a high-sensitivity, untargeted mass spectrometry metabolomics workflow.     

Relationship between physico-chemical properties of magnetic fluids and their heating capacity

Abstract

The final goal in magnetic hyperthermia research is to use nanoparticles in the form of a colloidal suspension injected into human beings for a therapeutic application. Therefore the challenge is not only to develop magnetic nanoparticles with good heating capacities, but also with good colloidal properties, long blood circulation time and with grafted ligands able to facilitate their specific internalisation in tumour cells. Significant advances have been achieved optimising the properties of the magnetic nanoparticles, showing extremely large specific absorption rate values that will contribute to a reduction in the concentration of the magnetic fluid that needs to be administered. In this review we show the effect of different characteristics of the magnetic particles, such as size, size distribution and shape, and the colloidal properties of their aqueous suspensions, such as hydrodynamic size and surface modification, on the heating capacity of the magnetic colloids.     

A fruit fly in the nanoworld: once again Drosophila contributes to environment and human health

Abstract

Studies were carried out to assess the effects of coating applied to zero-valent nano-iron (nZVI) on early life stage development of three key marine invertebrate species Mytilus galloprovincialis, Ciona intestinalis and Psammechinus milliaris. Embryo development was assessed following a 2-h exposure of the sperm to concentrations of two nZVIs of up to 10 mg l^-1 followed by in vitro fertilisation. Disruption of embryo development was most severe in sea squirts followed by mussel, while the urchin embryos were not significantly affected as compared with controls. An over twofold decrease in fertilisation success alongside significant delay in the embryo development was observed, and the effect was more severe with the coated form, possibly owing to its better colloidal stability. We provide in vitro evidence for the rapid dissolution (within 2 h) of nZVI in seawater to a degree that concentration of total solute Fe released from the coated ZVI particles exceeds safe limits of NOECs established for dissolved Fe.     

Nanoformulation of natural products for prevention and therapy of prostate cancer

There is a need for developing improved therapeutic options for the management of prostate cancer, able to inhibit proliferation of precancerous and malignant lesions and/or to improve the effectiveness of conventional chemopreventive and chemotherapeutic agents. In this perspective, application of nanotechnology based strategies for the delivery of natural compounds for effective management of the disease is being actively researched. Here, after highlighting the most promising natural compounds for chemoprevention and chemotherapy of prostate cancer, the state of the art nanotherapeutics and the recent proof-of-concept of “nanochemoprevention”, as well as the clinical development of promising targeted nanoprototypes for use in the prostate cancer treatment are being discussed.     

A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials

Engineered nanomaterials (ENM) are a growing aspect of the global economy, and their safe and sustainable development, use, and eventual disposal requires the capability to forecast and avoid potential problems. This review provides a framework to evaluate the health and safety implications of ENM releases into the environment, including purposeful releases such as for antimicrobial sprays or nano-enabled pesticides, and inadvertent releases as a consequence of other intended applications. Considerations encompass product life cycles, environmental media, exposed populations, and possible adverse outcomes. This framework is presented as a series of compartmental flow diagrams that serve as a basis to help derive future quantitative predictive models, guide research, and support development of tools for making risk-based decisions. After use, ENM are not expected to remain in their original form due to reactivity and/or propensity for hetero-agglomeration in environmental media. Therefore, emphasis is placed on characterizing ENM as they occur in environmental or biological matrices. In addition, predicting the activity of ENM in the environment is difficult due to the multiple dynamic interactions between the physical/chemical aspects of ENM and similarly complex environmental conditions. Others have proposed the use of simple predictive functional assays as an intermediate step to address the challenge of using physical/chemical properties to predict environmental fate and behavior of ENM. The nodes and interactions of the framework presented here reflect phase transitions that could be targets for development of such assays to estimate kinetic reaction rates and simplify model predictions. Application, refinement, and demonstration of this framework, along with an associated knowledgebase that includes targeted functional assay data, will allow better de novo predictions of potential exposures and adverse outcomes.     

松果菊苷固体脂质纳米粒处方筛选的研究

[目的] 探索不同辅料对于松果菊苷固体脂质纳米粒(SLN)理化性质的影响,从而对水溶性药物单体固体脂质纳米粒的处方研究做出一点提示。[方法] 采用单一变量法摸索松果菊苷SLN中Myrj52、山嵛酸甘油酯(Compritol 888 ATO)、单硬脂酸甘油酯、大豆卵磷脂等辅料对纳米粒理化性质的影响。[结果] 随Myrj52量的增加,纳米粒的粒径减小,Zeta电位增大,包封率增大。随Compritol 888 ATO量的增加,包封率降低,粒径稍有增大,Zeta电位减小。随单硬脂酸甘油酯量的增加,粒径明显增大,包封率略有减小,Zeta电位减小。随卵磷脂量的增加,粒径明显增大,电位明显减小。包封率降低。[结论] 各种辅料单独对松果菊苷SLN的理化性质都有较大影响,此研究可以为相似性质的药物SLN的处方筛选提供启示。     

介孔二氧化硅纳米粒增溶型非诺贝特片剂的制备及体内外研究

目的 制备介孔二氧化硅纳米粒(mesoporous silica nanoparticles,HK)增溶型非诺贝特(fenofibrate,FNB)片剂并进行体内外研究。方法 用吸附法以HK为FNB的载体制成固体分散体(FNB-HK)。采用差示扫描量热法、X射线衍射法和傅里叶红外光谱法分析非诺贝特在FNB-HK中的存在状态。通过考察体外溶出度,优化处方并制片。将自制片和市售片分别对家兔单剂量口服给药,采用高效液相色谱法测定家兔血浆药物浓度。结果 FNB-HK表征表明HK能够抑制非诺贝特的结晶。经过处方优化,乳糖做填充剂,8%羧甲基淀粉钠为崩解剂时,片剂能够达到最理想的溶出速率。自制片与市售片相比,体内达峰时间提前,达峰浓度增大,相对生物利用度为149.95%。结论 本研究研制的片剂能显著改善FNB的溶出速率,提高其口服生物利用度。