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 and pharmacodynamic features can be specifically tuned by including peptide functional elements as NG components. This study explores the formulation, decoration strategies, and structural properties of NGs derived from mixed hydrogel (HG) 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 sorbitane monooleate 80 (SPAN 80) as 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 (FT-IR) and Small-Angle X-ray Scattering (SAXS) technique. Different formulative routes were used and mutually compared to encapsulate or adsorb AlexaFluor 430 (succinimidyl ester), used as model of an anionic, pharmaceutical agent. In vitro experiments demonstrated good cytocompatibility of these systems and the release of AlexaFluor 430 was also evaluated.