Drug delivery systems are defined as formulations aiming for transportation of a drug to the desired area of action within the body. The basic component of drug delivery systems is an appropriate carrier that protects the drug from rapid degradation or clearance and thereby enhances drug concentration in target tissues. Based on their biodegradable, biocompatible, and nonimmunogenic structure, niosomes are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. In recent years, numerous research articles have been published in scientific journals reporting the potential of niosomes to serve as a carrier for the delivery of different types of drugs. The present review describes preparation methods, characterization techniques, and recent studies on niosomal drug delivery systems and also gives up to date information regarding recent applications of niosomes in drug delivery.

Niosomes are non-ionic surfactant-based vesicles with high promise for drug delivery applications. They can be rapidly prepared via microfluidics, allowing their reproducible production without the need of a subsequent size reduction step, by controlled mixing of two miscible phases of an organic (lipids dissolved in alcohol) and an aqueous solution in a microchannel. The control of niosome properties and the implementation of more complex functions, however, thus far are largely unknown for this method. Here we investigate microfluidics-based manufacturing of topotecan (TPT)-loaded polyethylene glycolated niosomes (PEGNIO). The flow rate ratio of the organic and aqueous phases was varied and optimized. Furthermore, the surface of TPT-loaded PEGNIO was modified with a tumor homing and penetrating peptide (tLyp-1). The designed nanoparticular drug delivery system composed of PEGNIO-TPT-tLyp-1 was fabricated for the first time via microfluidics in this study. The physicochemical properties were determined through dynamic light scattering (DLS) and zeta potential analysis. In vitro studies of the obtained formulations were performed on human glioblastoma (U87) cells. The results clearly indicated that tLyp-1-functionalized TPT-loaded niosomes could significantly improve anti-glioma treatment.

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (Fe_xO_y-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

The development of nanoscale drug delivery systems, which can mediate efficient tumor targeting together with high cellular internalization, is crucial for glioma treatment. The combination of therapeutic agents in nanoparticles provides synergistic effects and allows further surface modifications with targeting ligands for specific glioma therapy. To achieve this goal, both doxorubicin and curcumin were encapsulated in polyethylene glycolated niosomes (PEGNIO). The surface of co-drug loaded PEGNIO was modified with tumor homing and penetrating peptide (tLyp-1). Physicochemical properties were determined via dynamic light scattering (DLS) and spectral analysis. Moreover, flow cytometry studies were performed to examine the specific cellular uptake of the tLyp-1 targeted niosomal formulation. In vitro cytotoxicity and inhibition of tumor-like spheroids growth were investigated on human glioblastoma (U87) and human mesenchymal stem cells (hMSC) cells. The results clearly indicated that the strategy by co-administration of doxorubicin and curcumin with tLyp-1 functionalized niosomes could significantly improve anti-glioma treatment.

The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.

The ECETOC NanoApp was developed to support industry in the registration of sets of nanoforms, as well as regulators in the evaluation of these registration dossiers. The ECETOC NanoApp uses a systematic approach to create and justify sets of similar nanoforms, following the ECHA guidance in a transparent and evidence-based manner. The rational and decision rules behind the ECETOC NanoApp are described in detail in “Janer, G., R. Landsiedel, and W. Wohlleben. 2021. [Rationale and Decision Rules Behind the ECETOC NanoApp to Support Registration of Sets of Similar Nanoforms within REACH. Nanotoxicology 15 (2): 145–122. https://doi.org/10.1080/17435390.2020.1842933]”. The decision criteria apply to human health and environmental hazards and risks. Here, we focus mostly on human health hazards; the decision rules are applied to a series of case studies, each consisting of real nanoforms: two barium sulfate nanoforms, four colloidal silica nanoforms, eight ceria nanoforms, and four copper phthalocyanine nanoforms. For each of them, we show step by step how the ECETOC NanoApp rules are applied. The cases include nanoforms that are justified as members of the same set of similar nanoforms based on sufficient similarity of their intrinsic properties (Tier 1). They also include other nanoforms with a relatively high (but insufficient) similarity of intrinsic properties; their similarity could be justified by functional properties (Tier 2). The case studies also include nanoforms that are concluded not to belong to the same set of similar nanoforms. These outcomes of the NanoApp were overall consistent (sometimes conservative) with available in vivo data. We also noted that datasets for various nanoforms were limited and use of the NanoApp may require the generation of data relevant to the decision criteria.