Nano-in-micro electronspun membrane: merging nanocarriers and microfibrous scaffold for long-term scar inhibition

Abstract

The development of general strategies for efficiently loading drugs with distinct physicochemical properties, for example, hydrophilicity, lipophilicity and hydrophobicity, is currently a great challenge in the field of drug delivery. In this work, a poly (N-isopropyl acrylamide) (PNIPAAm) nanoparticle with reversible hydrophilic-to-hydrophobic property was first prepared. Owing to the switchable property of the PNIPAAm particles, all the water-soluble, lipo-soluble and poorly soluble drugs could be successfully loaded in the PNIPAAm particles. Then, these drug-loaded PNIPAAm nanoparticles could be introduced into electronspun fibrous as a medical scaffold. Another advantage of such two-stage drug loading strategy is that an extended release of the loaded drug would be achieved. We also found that the preparation of this nano-in-micro system also showed negligible effects on the drug loading ratio and drug activity, probably due to the mid and efficient nature of this approach. Moreover, the nano-in-micro scaffold exhibits excellent drug release characteristics such as a slow and persistent drug delivery for up to 4 months. A preclinical application of this 20S-Ginsenoside Rg3-loaded nano-in-micro scaffold showed a pronounced hypertrophic scar (HS) inhibitory effect in both early-stage and later-stage of HS formation. In short, the nano-in-micro scaffold with reversible hydrophilic-to-hydrophobic property in the drug-loaded nanoparticles would provide a facile, effective and general strategy to fabricate diverse drug delivery system with long-term release.