Development of a Nanoparticle Construct for the Delivery of Hydrophilic Peptide Drugs

Abstract

Although biologics have emerged as promising field of research and development in the pharmaceutical industry, delivery of this class of drugs has proven challenging due to enzymatic, immune, and renal clearance in circulation. Flash NanoPrecipitation (FNP) is a newly developed method for the formation of small, monodisperse polymeric nanoparticle drug carriers. FNP studies so far have primarily focused on the encapsulation of hydrophobic drugs. A proposed method of applying of this technique to hydrophilic peptides involves the creation of “inverse” particles with a hydrophilic core and hydrophobic corona followed by coating with a second protective layer containing a poly(ethylene glycol) (PEG) brush. FNP proved to be a successful technique for both the production of small, monodisperse poly(n-butylacrylate-block-acrylic acid) micelles suspended in chloroform anti-solvent and subsequent coating of the micelles with PEG. Micelle stability in water-miscible organic solvent prior to the second FNP step was achieved by cross-linking of the poly(acrylic acid) core with the chromium (III) cation. The successful development of this nanoparticle construct demonstrates great promise for a new effective mechanism of hydrophilic peptide drug delivery.