Collagen scaffold-mediated delivery of NLC/siRNA as wound healing materials

Abstract

Achieving prolonged and localized delivery of small interfering RNA (siRNA) at a specific site is highly desirable, since siRNA therapy has become a promising strategy for many medical applications. Many different synthetic or natural biomaterials have been studied for local sustained drug delivery. Of those, collagen has received increased attention, especially for wound applications, due to its biocompatibility, safety, and hemostatic properties. Therefore, we here investigated freeze-dried collagen scaffolds as localized siRNA delivery systems. Because siRNA faces significant difficulty in crossing biological membranes, efficient nanocarriers have been fabricated from synthetic or natural materials, such as chitosan (CS) and nanostructured lipid carriers (NLC). Collagen scaffolds were loaded with either naked siRNA or NLC/siRNA complexes, formed with cationic NLC comprising either a chitosan coating (CS-NLC), or DOTAP (1,2-dioleoyl-3-trimethylammonium-propan) and DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine) shell (cNLC). siRNA or NLC/siRNA loading did not affect collagen scaffold properties (structure and swelling ratio). Collagen loaded with cNLC nanoparticles achieved the most prolonged siRNA release and in vitro downregulation of ERK-1 protein (at least 7 days), which is involved in proliferation and wound healing. In conclusion, lipid nanoparticle templates were useful in prolonging and promoting siRNA delivery from collagen scaffolds.