Verification of nanoparticle formation, skin permeation, and apoptosis using nobiletin as a methoxyflavonoid derivative

Abstract

PurposeNobiletin (NOB), a polymethoxyflavonoid, is known for its antioxidant and anti-inflammatory effects and has antitumor activity. However, its poor solubility and low bioavailability pose a significant challenge in its delivery. In this experiment, NOB was added to Soluplus® (Sol)/l-ascorbyl 2,6-dipalmitate (ASC-DP) as a ternary system, and Sol/ASC-DP/NOB nanoparticles were obtained using the hydration method. The purpose of this study was to enhance the solubility of NOB, apply it for skin permeation, and improve antitumor activity.MethodsThe preparation of Sol/ASC-DP/NOB nanoparticles was attempted using the hydration method, and particle size, zeta potential, and stability tests were performed to evaluate the formation of nanoparticles. 1H-1H NOESY/ROESY NMR spectral measurements were also performed to identify molecular interaction between NOB and Sol/ASC-DP. To evaluate its functionality, DPPH radical scavenging, skin permeation, fluorescence microscopy, and cell viability analyses were performed.ResultsThe particles were approximately 100 nm in size in the ternary system (weight ratio (Sol/ASCDP/NOB=8/1/1)) and were relatively stable for approximately 7 days at 25 °C under light-shielded conditions. From the NMR spectrum measurements of Sol/ASCDP/NOB, a cross-peak was observed between the –OCH3 group: C6,8 (3.8 ppm) derived from NOB, the methyl group (2.0 ppm) derived from Sol, and the side chain portion (1.2 ppm) derived from ASC-DP. Cross-peaks were observed between the polyethylene glycol (PEG) backbone of Sol (3.6 ppm) and the side chain of ASC-DP (0.8–1.2 ppm). The formation of Sol/ASC-DP/NOB nanoparticles facilitated its skin permeation, and fluorescence microscopy confirmed improved permeation. The DPPH radical scavenging test revealed that Sol/ASC-DP/NOB had an IC50 of 46.7 μg/mL. Cell viability assays showed a 20–40% decrease in cell viability with the addition of Sol/ASC-DP/NOB at 0.1 mg/mL.ConclusionSol/ASC-DP/NOB nanoparticles were successfully prepared, and these were found to inhibit melanin formation and have antitumor activity.