Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

Abstract

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection-based delivery of insulin. Neonatal Fc receptor (FcRn)-mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn-targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH-responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH-sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn-targeted NPs. Overall, these FcRn-targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.

Plasma proteins facilitates placental transfer of polystyrene particles

“…Additionally, caveolae-mediated endocytosis of 100 nm fluorescent PS-particles was shown to be dependent on the abundance of albumin on the corona surface, supporting the idea that it might be an important driver for cellular uptake of PS-particles [61]. Our additional results with HSA containing media are an extension to studies demonstrating NP transfer by using cell barrier systems in the presence of albumin [58,59].…”

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

“…One of the most exciting strategies of functionalized PNs is the use of natural or synthetic polymers with different targeting ligands to provide specificity for organs or tissues, thus improving the uptake of nanoparticles from, for example, the gastrointestinal tract when oral administration is employed, the preferred drug administration pathway among the population. This strategy is relevant, as ligands and certain polymers have shown enhancing oral absorption [ 198 , 199 ]. Moreover, PNs built of stimulus-sensitive polymers and polymers with tuned structural features can be designed with on-demand functions including endosomal scape, high drug loading capacity, prolonged blood circulation and enhanced cellular uptake, among others [ 58 , 200 ].…”

All-in-one microfluidic assembly of insulin-loaded pH-responsive nano-in-microparticles for oral insulin delivery

“…In fact, the degradation of proteins and peptides under acidic conditions in the stomach concomitantly with digestive enzyme action, as well as the poor oral bioavailability, characterized by a poor protein permeability in the intestinal epithelium [7][8][9] has led to the need for designing and developing alternative approaches to enhance the oral protein/peptide administration. [10][11][12] Over the last decade, the research for different strategies for the oral delivery of proteins and peptides, such as microemulsions, 13,14 polymeric nanoparticles, 8,9,16 silicon nanoparticles 15,17,18 and liposomes, 19,20 has been significantly increasing. Liposomes, introduced for the first time by Bangham et al 21 at the beginning of the 1960s, have been described as potential protein and peptide drug carriers able to enhance their blood residence time and targeting.…”