Lipid Nanoparticles: encapsulation of Polysaccharides

Lipid Nanoparticles (LNPs) are constructed with a lipid shell encompassing a core composed of reverse micelles encapsulating drugs, all within a diameter of about 100 nm. The lipid components typically consist of ionizable lipid, phospholipid, cholesterol, and PEGylated lipid.1 Recently the interest, as well as the number of approved drugs formulated with LNPs strategy, is increasing due to several advantages, such as the delivery of hydrophobic and hydrophilic drugs, the controlled release, the reduction of drugs adverse effects, the biocompatibility, and the increase of drug lifetime.1 Polysaccharides are heterogeneous group of natural polymers, characterized by biocompatibility, biodegradability, and nontoxicity, coupled with wide availability and usually low costs. Numerous studies have demonstrated the biological activities of polysaccharides and particularly of charged polysaccharides, such as anti-tumoral, anti-inflammatory, anti-virals, anti-coagulant, immunomodulatory and antimicrobial properties. 2 Due to the growing interest towards polysaccharides in pharmaceutical fields, we decided to formulate LNPs containing polysaccharides. The LNPs formulations were obtained using a microfluidic system, which guarantee an excellent size control, a great homogeneity and repeatability, with the possibility to achieve volumes from µL to L and an optimal sample consumption. Furthermore, formulations would allow also to optimize the routes of administration - often a critical point for carbohydrates. Various polysaccharides and derivatives, characterized by different molecular weight and charge, such as heparin, pentosan polysulphate and hyaluronic acid, have been selected for the encapsulation in LNPs. Size and Zeta potential, determined by Dynamic Light Scattering, of the LNPs confirmed a size compatible with pharmaceutical applications (< 100 nm), good homogeneity and stability over time. The encapsulation efficiency is determined by Size Exclusion Chromatography. The results are encouraging in terms of efficacy and quantity of encapsulated polysaccharides. LNPs-polysaccharides formulations have been characterized by Nuclear Magnetic Resonance and Fluorescent Spectroscopy. Finally, preliminary structural studies have been carried out using electronic scanning techniques (TEM and SEM) and Small Angle X-Ray Scattering.