Novel high yield and continuous process in manufacturing of nanoliposomes covered by polymeric thin layer

Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Nowadays the most common techniques used for the production of liposomal delivery systems, such as Freeze-thawing, Thin film hydration, Ethanol injection, and Reverse phase evaporation, are all characterized by bulk discontinuous processes and low productivity. Moreover drastic conditions (such as low/high temperatures and pressures) make these techniques energetically onerous. In order to produce higher volumes of liposomal vectors, directly on nanometric size, overcoming the operating limits above discussed, a robust, simple, and easy-to-transfer technology was realized. In particular, a novel continuous bench scale apparatus was designed and developed, by exploiting microfluidics principles transposed on a millimeter scale, and coupling it with an ultrasound process used as intensification tool for vesicles homogenization. Moreover, the same innovative continuous method, based on microfluidic principles, was used to achieve wrapping of liposomes by chitosan (a natural biocompatible polymer) to overcome some typical drawbacks of liposomes, such as poor stability into biological fluids as well as in stocking conditions, and to manufacture stable shell-core nanostructures.