Enhanced encapsulation and membrane retention of Teleogryllus mitratus protein via hydrophobic ion-pairing in nanostructured lipid carriers

This study aimed to enhance the topical delivery of Teleogryllus mitratus protein hydrolysate (TM) by forming hydrophobic ion-pair (HIP) complexes with dioctyl sodium sulfosuccinate (DS) and incorporating them into lipid-based nanocarriers. TM was extracted via an enzyme-assisted method and complexed with DS to form TM-HIP. Chitosan nanoparticles (CNP), nanoemulsions (NE), and nanostructured lipid carriers (NLC) containing TM or TM-DS were prepared and characterized for particle size, polydispersity, zeta potential, encapsulation efficiency (EE), loading capacity (LC), and in vitro release. Membrane retention was assessed using Strat-M® membranes in Franz diffusion cells. The results showed that TM successfully formed a HIP complex with DS, resulting in an increased diffusion coefficient. All nanocarriers exhibited nanoscale particle sizes (~70–300 nm), narrow distributions (PDI 0.17–0.26), and stable zeta potentials (−30 to −37 mV). Lipid-based nanocarriers containing TM-DS demonstrated the highest EE (TM-DS-NE: 76.8 ± 0.5%; TM-DS-NLC: 81.9 ± 2.4%) and sustained release, while CNP showed lower EE (17.6 ± 3.1%). Membrane retention studies revealed that TM-DS-NE (49.9 ± 0.7 μg/cm 2 ) and TM-DS-NLC (50.1 ± 3.1 μg/cm 2 ) achieved significantly higher protein deposition than TM-CNP (1.6 ± 0.8 μg/cm 2 ), TM-NE (6.4 ± 1.2 μg/cm 2 ), TM-NLC (9.2 ± 1.7 μg/cm 2 ), or TM solution (1.2 ± 0.7 μg/cm 2 ), with NLC identified as the most effective carrier. Therefore, it can be concluded that hydrophobic ion-pairing of TM with DS enhanced compatibility with lipid-based nanocarriers, resulting in improved encapsulation and membrane retention. The combination of protein lipophilicity, carrier composition, and nanoscale size effectively promoted delivery into the Strat-M® membranes. Further clinical studies are recommended to validate efficacy and safety under physiologically relevant conditions. • T. mitratus protein hydrolysate (TM) was a bioactive protein for topical use. • Hydrophobic ion-pairing (HIP) with sodium docusate (DS) enhanced TM lipophilicity. • TM–DS complexes enabled efficient incorporation into lipid-based nanocarriers. • Nanoemulsions and nanostructured lipid carriers (NLC) were achieved. • TM–DS–NLCs enabled improved protein retention in Strat-M® membranes.