Evaluation of cationic peptide-based nanogels as delivery systems for negatively charged molecules: a formulative study

Peptide-based nanogels (NGs) represent a cutting-edge class of nanoscale drug delivery systems. Due to their structural properties, NGs platforms can encapsulate and protect therapeutic agents ( e.g. peptides, proteins, and nucleic acids), while allowing for controlled and stimuli-responsive release. These pharmacokinetic/pharmacodynamic features can be specifically modified including peptide functional elements as NGs component. This study explores the formulation, decoration strategies, and structural properties of NGs derived from mixed hydrogel matrices of Fmoc-diphenylalanine (Fmoc-FF) with cationic amphiphilic peptides (CAPs). CAPs, composed by cationic hexapeptide (GK)3 sequence decorated at its N -terminus with alkyl chain, were found able to confer a net positive charge to Fmoc-FF NGs. Fmoc-FF/C16-(GK)3 and Fmoc-FF/C18-(GK)3 NGs were obtained using polysorbate 80 (TWEEN ^® 80) and sorbitan monostearate 80 (SPAN ^® 80) colloidal stabilizing surfactants and characterized in terms of size, secondary structure, superficial charge and shelf stability by Dynamic Light Scattering (DLS), Circular Dichroism (CD), Fourier Transform Infrared (FTIR) and SAXS technique. Different formulative routes were applied and mutually compared to encapsulate/adsorb Alexa Fluor ^TM 430 (succinimidyl ester), used as model of an anionic, pharmaceutical agent. In vitro experiments demonstrate a good cytocompatibility of these systems and the release of Alexa Fluor ^TM 430 was also evaluated.