Niosomes as Drug Nanovectors: Multiscale pH-Dependent Structural Response

Abstract

The use of nanocarriers, which respond to different stimuli controlling their physicochemical properties and biological responsivness, shows a growing interest in pharmaceutical science. The stimuli are activated by targeting tissues and biological compartments, e.g., pH modification, temperature, redox condition, enzymatic activity, or can be physically applied, e.g., a magnetic field and ultrasound. pH modification represents the easiest method of passive targeting, which is actually used to accumulate nanocarriers in cells and tissues. The aim of this paper was to physicochemically characterize pH-sensitive niosomes using different experimental conditions and demonstrate the effect of surfactant composition on the supramolecular structure of niosomes. In this attempt, niosomes, made from commercial (Tween21) and synthetic surfactants (Tween20 derivatives), were physicochemically characterized by using different techniques, e.g., transmission electron microscopy, Raman spectroscopy, and small-angle X-ray scattering. The changes of niosome structure at different pHs depend on surfactants, which can affect the supramolecular structure of colloidal nanocarriers and their potential use both in vitro and in vivo. At pH 7.4, the shape and structure of niosomes have been maintained; however, niosomes show some differences in terms of bilayer thicknesses, water penetration, membrane coupling, and cholesterol dispersion. The acid pH (5.5) can increase the bilayer fluidity, and affect the cholesterol depletion. In fact, Tween21 niosomes form large vesicles with lower curvature radius at acid pH; while Tween20-derivative niosomes increase the intrachain mobility within a more interchain correlated membrane. These results demonstrate that the use of multiple physicochemical procedures provides more information about supramolecular structures of niosomes and improves the opportunity to deeply investigate the effect of stimuli responsiveness on the niosome structure.

Deciphering the Role of Bilayer of a Niosome towards Controlling the Entrapment and Release of Dyes

“…The introduced disorderness due to structural changes in the bilayer region, were convincingly detected using this technique. The parameters like intermolecular chain coupling, packing order and freedom of motion of the terminal methyl groups were taken into account while examining the bilayer structure of the niosome as discussed in the following section.…”

pH-sensitive niosomes: Effects on cytotoxicity and on inflammation and pain in murine models

“…Loaded bilayers can close in smaller, highly curved particles, thanks to the presence within the bilayer of an additional component, the drug, that can be distributed non-uniformly both laterally and transversely inside the hydrophobic core. Moreover, in TW20 and TW20-GLY, self-assembled niosomes cholesterol can be partially excluded from the bilayer or can be present in the form of crystallites 33 , 34 . The presence of an additional amphiphilic component may change the amount and the distribution of cholesterol within the two leaflets of the bilayers.…”

“…The best behavior in “ in vitro ” release experiments of pH-sensitive vesicles (samples TW20-GLY 5% LIDO and TW20-GLY 5% IBU, Table 1 ) was confirmed in “ in vivo ” experiments in murine models highlighting the potential advantages of stimuli responsive nanocarriers in pain and inflammation treatments. Niosomes containing pH-sensitive components, such as TW20-GLY that protonate at lower pH, show a destabilization of the carrier bilayer, probably due to the segregation or leakage of cholesterol 33 .…”

Cyclodextrin modified niosomes to encapsulate hydrophilic compounds

“…13 Niosomes are microscopic vesicles formed by non-ionic surfactants which form closed bilayer structures due to their amphiphilic nature. 16,17 The lipophilic groups are located within the membrane while the hydrophilic groups are exposed to the aqueous medium 18,19 as in liposomes. Non-ionic surfactants are preferred in comparison with ionic ones due to their ability to increase the solubility of highly water insoluble compounds, 20 great compatibility with biological systems (lower toxicity, less irritation effect and non-immunogenicity), 21 improved chemical stability against oxidation, and feasibility of surface modication.…”