No abstract

Transdermal drug delivery (TDD) is an advantageous and effective approach for the localized delivery of drugs; however, overcoming the high impermeability of the outermost layer of skin, the stratum corneum, represents a significant challenge to TDD. Herein, we describe a simple and biocompatible platform based on a two-component molecular hydrogel for the transdermal delivery of the non-steroidal anti-inflammatory drug (S)-naproxen. The hydrogel is formed by two amphipathic tetrapeptides bearing aromatic side groups and oppositely-charged residues that co-assemble into fibrillar networks at pH 7.4. We demonstrate that (S)-naproxen, which possesses an aromatic region and an ionizable group, can be effectively loaded into the hydrogel. We characterized drug-loaded hydrogels by NMR and rheology and studied in vitro release under physiologically relevant conditions. Moreover, TDD studies on human skin samples demonstrated a twofold increase in the permeation of (S)-naproxen, which could be advantageous for the localized delivery of the drug.

While coronary angioplasty represents an effective treatment option following acute myocardial infarction, the reperfusion of the occluded coronary artery can prompt ischemia–reperfusion (I/R) injury that significantly impacts patient outcomes. As ω‐3 polyunsaturated fatty acids (PUFAs) have proven, yet limited cardioprotective abilities, an optimized polymer‐conjugation approach is reported that improves PUFAs bioavailability to enhance cardioprotection and recovery in animal models of I/R‐induced injury. Poly‐l‐glutamic acid (PGA) conjugation improves the solubility and stability of di‐docosahexaenoic acid (diDHA) under physiological conditions and protects rat neonatal ventricular myocytes from I/R injury by reducing apoptosis, attenuating autophagy, inhibiting reactive oxygen species generation, and restoring mitochondrial membrane potential. Enhanced protective abilities are associated with optimized diDHA loading and evidence is provided for the inherent cardioprotective potential of PGA itself. Pretreatment with PGA–diDHA before reperfusion in a small animal I/R model provides for cardioprotection and limits area at risk (AAR). Furthermore, the preliminary findings suggest that PGA–diDHA administration in a swine I/R model may provide cardioprotection, limit edema and decrease AAR. Overall, the evaluation of PGA–diDHA in relevant preclinical models provides evidence for the potential of polymer‐conjugated PUFAs in the mitigation of I/R injury associated with coronary angioplasty.