Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

Peptide encapsulation regulated by the geometry of carbon nanotubes

In this work the encapsulation of an α-helical peptide in single carbon nanotubes (CNTs) with similar diameter and length but different geometry (armchair and zigzag) was investigated through molecular dynamics simulations and free energy calculations. Our simulation results showed that in vacuo it makes no evident difference whether the investigated peptide is encapsulated in armchair or zigzag CNTs; however, in aqueous solution the armchair CNT encapsulates the peptide remarkably easier than the zigzag CNT does. A detailed analysis revealed that the equilibrium conformation of the water molecules inside the CNTs with varying geometry mediates the peptide encapsulation. It suggests that the water molecules play an important role in regulating behaviors of biomolecules in bio-systems. Then the impact of the CNT geometry on the conformational changes of the confined peptide was studied. Analyses of secondary structures showed the α-helix of the peptide could be better maintained in the zigzag CNT.     

Interaction of metal oxide nanoparticles with lung surfactant protein A

The alveolar lining fluid (ALF) covering the respiratory epithelium of the deep lung is the first biological barrier encountered by nanoparticles after inhalation. We here report for the first time significant differences for metal oxide nanoparticles to the binding of surfactant protein A (SP-A), the predominant protein component of ALF. SP-A is a physiologically most relevant protein and provides important biological signals. Also, it is involved in the lung’s immune defence, controlling e.g. particle binding, uptake or transcytosis by epithelial cells and macrophages. In our study, we could prove different particle-protein interaction for eight different nanoparticles, whereas particles of the same bulk material revealed different adsorption patterns. In contrast to other proteins as bovine serum albumin (BSA), SP-A does not seem to significantly deagglomerate large agglomerates of particles, indicating different adsorption mechanisms as in the well-investigated model protein BSA. These findings may have important consequences for biological fate and toxicological effects of inhaled nanomaterials.     

Influence of carboxylic acid functionalization on the cytotoxic effects induced by single wall carbon nanotubes on human endothelial cells (HUVEC)

A vast variety of nanomaterials have been developed in the recent years, being carbon nanotubes (CNTs) the ones that have attracted more attention, due to its unique properties which make them suitable for numerous applications. Consequently, it is predicted that tons of CNTs will be produced worldwide every year, being its exposure of toxicological concern. Nanomaterials, once into the body, can translocate from the uptake sites to the blood circulation or the lymphatic system, resulting in distribution throughout the body. Thus, the vascular endothelium can be in contact with them and can suffer from their toxic effects. In this regard, the aim of this work was to investigate the cytotoxicity of single-walled carbon nanotubes (SWCNTs) on human endothelial cells evaluating the influence of acid carboxylic functionalization and also the exposure time (24 and 48 h). Biomarkers assessed were neutral red uptake, protein content, a tetrazolium salt metabolization and cell viability by means of the Trypan blue exclusion test. Cells were exposed to concentrations between 0 and 800 μg/mL SWCNTs for 24 and 48 h. Results have shown that both SWCNTs and carboxylic acid functionalized single-walled carbon nanotubes (COOH-SWCNTs) induce toxic effects in HUVEC cells in a concentration- and time-dependent way. Moreover, the carboxylic acid functionalization results in a higher toxicity compared to the SWCNTs.     

Nanomaterials properties vs. biological oxidative damage: Implications for toxicity screening and exposure assessment

Biological oxidative damage (BOD) has been recognized as a key toxicity mechanism with potential as a novel global metric for nanomaterial (NM) exposure and rapid toxicity screening. A ‘Ferric reducing ability of serum (FRAS)’ assay, recently optimized by our group, was used to quantitate the degree of BOD induced by 19 diverse, commercially important NMs, including carbon blacks, fullerenes, carbon nanotubes, and titanium dioxide. This study investigated the relationship between several physico-chemical parameters of NMs and BOD and their relevance to exposure assessment and toxicity screening. FRAS-measured BOD strongly correlated with specific surface area and total content of select transition metals (especially Fe, Cr, Co, Mo and Mn). These two factors combined explained 93% of the BOD. The FRAS BOD potential of NMs appears to be a valid approach for screening purposes. These findings support the use of BOD as a metric for NM exposures.     

Advances in use of functionalized carbon nanotubes for drug design and discovery

Introduction: As a part of increasing interest in nanobiotechnology, nanoparticle-based drug discovery as well as development and drug delivery constitute an important area in nanomedicine, and it is also driven by search for new drugs by the pharmaceutical industry. Nanomaterials for pharmaceutical application include carbon nanotubes (CNTs).

Areas covered: This article describes the properties of CNTs, both single-walled CNTs (SWCNTs) and multiwalled CNTs (MWCNTs) with relevance to drug discovery and development. Pharmacokinetics of CNTs as well as CNT-based drug delivery is discussed. The article also looks at how the scope for pharmaceutical applications of CNTs is broadened by conjugation with other molecules and presents the potential therapeutic applications. Finally, the toxicology of CNTs is considered with measures under investigation for reducing it. Literature on CNTs, from the past 5 years, was reviewed and selected publications relevant to drug discovery, development, and delivery were included in the bibliography.

Expert opinion: Carbon nanotubes combine more properties relevant to drug development and delivery than any other nanomaterial. Although a tremendous amount of basic research has been done on CNTs during the past decade, little of this is nearing translation into human applications. No CNT-based medicine has reached clinical trials. Nevertheless, CNT conjugation with other molecules has extended the horizons for their potential therapeutic applications. The most promising of these is PEGylation, which extends the survival of CNTs in circulation. Potential future applications of CNTs include combination of diagnostics and therapeutic drug delivery as well as a component of multimodal therapies for tissue regeneration.     

碳纳米管/羟基磷灰石复合材料的制备研究

通过研究球磨工艺、超声分散工艺以及超声分散结合滴定工艺三种制备CNTs/HAp复合粉体的工艺,认为以纯超声分散工艺效果最佳.根据DSC曲线确定了两种烧结曲线.经冷压成型、冷等静压成型,600℃真空热处理结合真空或Ar保护无压烧结制备出了CNTs/HAp复合材料.加入CNTs后CNTs/HAp复合材料的弯曲强度与断裂韧性都有提高,但提高的幅度不同.通过TEM、SEM观察了复合材料的粉体及断口情况,确定出了一个合理的CNTs/HAp复合材料的制备工艺.     

g-C3N4纳米棒/TiO2/Ni/CNTs复合物的制备及其光催化性能

通过简单的快速加热回流本体氮化碳制备了缺陷较少的g-C₃N₄纳米棒;然后采用缓慢水解法在g-C₃N₄纳米棒表面负载掺杂镍的TiO₂前驱体,经热处理制得g-C₃N₄纳米棒/TiO₂/NiO纳米复合光催化剂;最后以TiO₂中的Ni为催化剂,采用化学气相沉积法原位生长CNTs,制备g-C₃N₄纳米棒/TiO₂/Ni/CNTs纳米复合光催化剂。通过XRD、TG、TEM、FT-IR、UV-Vis等测试方法对催化剂进行表征,考察了样品在紫外光和可见光下对亚甲基蓝（MB）的光催化降解活性。结果表明：g-C₃N₄纳米棒/TiO₂/Ni/CNT纳米复合物在紫外和可见光下对亚甲基蓝的降解率分别为87%和68%,光催化活性较g-C₃N₄/TiO₂/NiO有明显提高。     

Effects of water-soluble functionalized multi-walled carbon nanotubes examined by different cytotoxicity methods in human astrocyte D384 and lung A549 cells

The widespread projected use of functionalized carbon nanotubes (CNTs) makes it important to understand their potential harmful effects. Two cell culture systems, human A549 pneumocytes and D384 astrocytoma cells, were used to assess cytotoxicity of multi-walled CNTs (MWCNTs) with varying degrees of functionalization. Laboratory-made highly functionalized hf-MW-NH₂ and less functionalized CNTs (MW-COOH and MW-NH₂) were tested in comparison with pristine MWCNTs, carbon black (CB) and silica (SiO₂) by MTT assay and calcein/propidium iodide (PI) staining. Purity and physicochemical properties of the test nanomaterials were also determined.     

Ag nanoparticles decorated electrospinning carbon nanotubes/polyamide nanofibers

Abstract

Antibacterial composite nanofibers have recently been widely applied in biomedical fields. The purpose of this study is to combine Polyamide66 (PA) with carbon nanotubes (CNTs) and Ag nanoparticles through electrospinning and the aqueous reduction method to synthesis Ag@CNT/PA composite nanofibers with excellent conductivity, antibacterial property and cytocompatibility. The morphology and structure of Ag@CNT/PA composite nanofibers were analyzed by a series of characterizations. Conductivity of Ag@CNT/PA composite nanofibers in wet state was measured using a four-probe resistance tester. The antibacterial activity of Ag@CNT/PA composite nanofibers was tested by inhibition zone method, and the MG-63 cells were used to detect the cytotoxicological effects of the composite nanofibers. The results show that the Ag nanoparticles (50–100?nm) are distributed uniformly on the surface of nanofibers. Conductivity of Ag@CNT/PA composite nanofibers reaches (9.918?±?0.043)?×?10^?4?S?mm^?1, significantly higher than that of PA nanofibers ((1.486?±?0.017)?×?10^?4?S?mm^?1). The Ag@CNT/PA composite fibers present good antibacterial activity against Escherichia coli and Staphylococcus aureus. Cell culture results show that the cell proliferation of Ag@CNT/PA composite nanofiber group seems no significant difference with PA nanofiber group (p?>?0.05) at day 7. The Ag@CNT/PA composite nanofibers have no significant negative effects on MG-63 cells.