Dual-labeled visual tracer system for topical drug delivery by nanoparticle-triggered P-glycoprotein silencing

Using nanoparticle-based drug delivery systems as enhancers is a robust strategy for transdermal delivery;however, the mechanisms by which these systems promote transdermal penetration are still unclear.Here, we fabricated a dual-labeled nano drug delivery system that allows discrete visualization of both the drug and the nanoparticle carrier. To comprehensively examine its potential mechanism, we investigated its effects on human epidermal keratinocyte Ha Ca T cells, including changes in cell membrane potential, intracellular Ca;concentration, and Ca;-ATPase activity. P-glycoprotein(P-gp) expression in nanoparticle-treated human dermal microvascular endothelial cells was detected by western blotting and immunofluorescence. Furthermore, the transdermal absorption and biodistribution of the dual-labeled nanoparticles were deeply investigated by skin permeability study in vitro and in vivo using fluorescence microscopy and in vivo imaging, respectively. In addition to reducing membrane potential, increasing the intracellular Ca;concentration, and decreasing Ca;-ATPase activity, our results indicate that the duallabeled nanoparticles can downregulate P-gp to promote transdermal absorption. Fluorescence and in vivo imaging visually demonstrated that the nanoparticle delivery system penetrated into the dermis through the stratum corneum. All these results indicate that this dual-labeled nano delivery system provides a new method for future in-depth visual explorations of transdermal drug delivery mechanisms.

Bottlebrush inspired injectable hydrogel for rapid prevention of postoperative and recurrent adhesion

Postsurgical adhesion is a common clinic disease induced by surgical trauma,accompanying serious subsequent complications.Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn’t effectively promote peritoneum repair.Herein,inspired by bottlebrush,a novel self-fused,antifouling,and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid(HA-GMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)monomer without any chemical crosslinkers,termed as H-HPMA hydrogel.The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time.Intriguingly,the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability.The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis in vivo.The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days.Furthermore,an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition(MMT)process dominated by the TGF-β-Smad2/3 signal pathway.Thus,we developed a simple,effective,and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis,offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.