From magic bullets to nanomedicine: where do we stand?

Targeted drug delivery (TDD) is an advanced version of Paul Ehrlich’s “magic bullet” concept (1907). In fact, it allows the direct delivery of the drug into its targeted body area to overcome off-target accumulation in the body related to the non-specificity of conventional drug delivery, increasing the bioavailability of the delivered drug, consequently reducing the amount of drug required for therapeutic efficacy [1]. Niosomes (NIOs) are promising nanoscale drug carriers composed mainly of surfactants. Like liposomes, they are stable and able to encapsulate both hydrophilic and lipophilic drugs, minimizing their degradation or inactivation after administration. The advantages in designing NIOs are less costs and more stability of surfactants instead of phospholipids composing liposomes. For this reason, NIOs may represent efficient and versatile therapeutic platform treatments. Due to the long production times and the high consumption of reagents, there was the need to develop a new production technique, such as microfluidics, that allows to process small amount of fluids but with the need to evaporate the organic solvent used, introducing purification methods that could reduce the amount of drug entrapped. Thanks to the fine control of the operating parameters, the reproducibility of the processes and low production times, it could be used to scale up from lab to full production. Additionally, the improved repeatability and reproducibility of the results could be used to obtain standardized information about nanocarriers characterization in the perspective of a marketing authorization [2]. The aim of this study was to design, prepare and characterize NIOs composed by Tween 21 and cholesterol by using two different preparation techniques: “Thin Layer Evaporation” (TLE) and “Microfluidic Technique” (MT), to investigate their influence on NIOs hydrodynamic diameter, polydispersity index and -potential. Additionally, NIOs stability and entrapment efficiency (E.E.) of two different probes were also investigated. In conclusion, the obtained results showed that the two preparation methods do not cause any changes in size and bilayer features of the obtained NIOs. NIOs obtained by MT or TLE are similar and able to load both hydrophilic and hydrophobic probes. Even if there is not a clearly better technique because each method has intrinsic advantages and disadvantages, the MT produces much more yield in shorter periods of time so it could represent a new approach to produce nanomedicines in the context of industrial scale-up. ____ [1] B. Vorrius, Z. Qiao, J. Ge, Q. Chen, Pharmaceuticals 2023, 16, 967. [2] D.A. Dri, F. Rinaldi, M. Carafa et al. Drug Delivery and Translational Research 2023, 13, 757–769.