Pharmacological Behavior of Propylene Glycol/Polyvinyl Alcohol Hydrogel Incorporating Indomethacin Nanocrystals in the Skin

BACKGROUND: We previously reported that carbopol hydrogels incorporating indomethacin nanoparticles (IMC NPs) improved the low permeability and bioavailability of skin formulations in transdermal drug delivery systems. However, the combination of NPs with other types of hydrogels has not been sufficiently explored to date. Therefore, this study investigated propylene glycol (PG)/polyvinyl alcohol (PVA) hydrogel as an alternative base to carbopol hydrogel for incorporating IMC NPs. METHODS: IMC NPs were prepared using bead milling treatment, and these NPs were incorporated into PG/PVA hydrogel (IMC-NP@PG/PVA hydrogel). The IMC concentration was measured using the HPLC method, and seven-week-old Wistar rats were used to evaluate skin absorption. RESULTS: Bead milling reduced the IMC particle size in the PG/PVA hydrogels to the nanoscale (30-200 nm) without altering its crystalline form. The IMC-NP@PG/PVA hydrogel exhibited enhanced uniformity, solubility, and drug release compared to the IMC microparticle-loaded PG/PVA hydrogel (IMC-MP@PG/PVA hydrogel), with a 1.44-fold greater area under the concentration-time curve. Transdermal permeability studies revealed that IMC-NP@PG/PVA had 2.36-fold higher absorption than the IMC-MP@PG/PVA hydrogel, with dissolved IMC permeating the skin. Pharmacokinetics in the rats showed significantly increased plasma levels, absorption rates, and bioavailability for IMC-NP@PG/PVA, demonstrating its superior delivery efficiency. Moreover, the skin absorption of IMC-NP@PG/PVA was higher than that of carbopol hydrogel. CONCLUSIONS: These findings highlight the potential of PG/PVA hydrogels as an effective base for transdermal drug delivery systems based on NPs.