Enhanced Targeted Drug Delivery for Scar Prevention: Clathrin‐Coated Solid Lipid Nanoparticles for Model Drug Encapsulation

Abstract Excessive scar formation is a major complication of wound healing. Premature release of anti‐scarring drugs can negatively impact healing. This study aims to develop a targeted delivery system for the controlled release of anti‐scarring drugs during the scar formation stage. Solid lipid nanoparticles (SLNs) coated with Clathrin, a cage‐like protein, to prevent premature drug release is developed. Insulin‐like growth factor (IGF) is conjugated to the SLNs for targeted delivery via its affinity for connective tissue growth factor (CTGF), a protein overexpressed during scar formation. The IGF‐Clathrin‐SLNs exhibited a size of 300 ± 20 nm and a zeta potential of 9.23 ± 0.4 mV. In vitro studies demonstrated sustained release of the encapsulated drug‐ kynurenic acid; less than 10% of kynurenic acid is released within three days, while over 50% is released within 10 h upon Clathrin removal using a surfactant at pH 8. Cellular uptake studies confirmed targeting efficacy. Fibroblasts with low CTGF expression displayed low uptake (<10%), whereas MCF7 cells with high CTGF expression showed significantly higher uptake (80%). This work demonstrates a promising targeted delivery platform for the controlled release of anti‐scarring drugs during scar formation.