Lactoferrin and Nanotechnology: New Perspectives and Therapeutic Applications for This Multifunctional Protein
Fabiana Superti, Alessia Mariano, Anna Scotto d’AbuscoLactoferrin, a multifunctional glycoprotein belonging to the transferrin family, is proving to be an extremely promising drug delivery vehicle, with numerous applications in the field of nanotechnology. This protein is biocompatible and well-tolerated and, regarding cell targeting, it is capable of binding to low-density lipoprotein receptor-related protein 1, a large multifunctional transmembrane receptor that mediates endocytosis, cell signaling, and protein clearance. Interestingly, lipoprotein receptor-related protein 1 is overexpressed in various cell types, particularly on tumor cells and blood–brain barrier endothelial cells. The purpose of this review is to summarize the most important beneficial activities demonstrated by lactoferrin nanoparticles obtained through various methods, aiming to identify potential prospects for their future applications in nanomedicine. Due to its remarkable stability and safety, interaction with specific cellular receptors, and ability to cross various key biological barriers in the human body, including the blood–brain barrier, lactoferrin has been successfully used to deliver therapeutic agents directly to their targets. This reduces systemic side effects while improving bioavailability and therapeutic outcomes. The main specific characteristics of lactoferrin nanoparticles include controlled release of the active ingredient at acidic pH, the ability to deliver hydrophobic drugs through various routes, and the greater efficacy and lower toxicity of the encapsulated drug compared to the free drug. This review highlights scientific evidence from in vitro and in vivo studies regarding the benefits of lactoferrin-based nanoformulations to enhance the therapeutic efficacy of molecules and drugs used to treat communicable and noncommunicable diseases. However, given that their practical application has remained rather limited to date, it is anticipated that lactoferrin nanoparticles will increasingly attract the attention of researchers across various fields, such as biology, medicine, and nanotechnology, with the aim of enabling their clinical application.