Peptide-Loaded Solid Lipid Nanoparticles Prepared through Coacervation Technique

Stearic acid solid lipid nanoparticles were prepared according to a new technique, called coacervation. The main goal of this experimental work was the entrapment of peptide drugs into SLN, which is a difficult task, since their chemical characteristics (molecular weight, hydrophilicity, and stability) hamper peptide-containing formulations. Insulin and leuprolide, chosen as model peptide drugs, were encapsulated within nanoparticles after hydrophobic ion pairing with anionic surfactants. Peptide integrity was maintained after encapsulation, and nanoparticles can act in vitro as a sustained release system for peptide. 1. Introduction The development of colloidal carrier systems in drug administration has attracted increasing attention during recent years as innovative strategy to overcome frequent therapy failures due to unpredictable bioavailability of drugs when administered by the conventional routes and in the conventional dosage forms. The most investigated systems are simple and multiple emulsions, liposomes, micelles, micro- and nanoparticles based on synthetic polymers or natural macromolecules [1]. Particularly, peptides and protein drugs represent a very important class of therapeutic agents, owing to the understanding of their role in physiology and pathology as well as to the advances in biotechnology and genetic engineering. Unfortunately, they are characterised by a short biological half-life, being easily degraded by proteolytic enzymes; moreover, most peptides poorly cross biological barriers due to their poor diffusivity and low partition coefficient. The entrapment of peptides and proteins into nanoparticulate systems still remains a difficult task, since each molecule is characterised by essential properties (e.g., molecular weight, hydrophilicity, and stability) that might be somehow different with respect to another one. This situation often hampers peptide-containing formulations, because each peptide becomes the subject of a case study. The choice of a correct formulation strategy is mainly driven by solubility and molecular stability considerations [2]. In the last twenty years, solid lipid nanoparticles (SLNs) have attracted increasing attention as efficient colloidal drug carriers, alternative to polymeric nanoparticles, with the advantage of being prepared with physiological and nontoxic lipids, used as common pharmaceutical excipients [3]. The use of lipids as matrix materials for sustained-release formulations for peptides and proteins has been reported only by a few authors [4, 5], owing to the hydrophobic nature of lipid