Cholesterol-functionalized polyacrylic acid as a stabilizer for vitamin D3 oil-in-water emulsions for topical application

Vitamin D-3 is essential for bone health, immune function, skin health and overall metabolism, but delivering it effectively remains a challenge. When taken orally, its poor solubility, low bioavailability, and instability often limit its effectiveness. Topical delivery could offer an attractive alternative particularly for skin targeting, but this requires stable formulations that can protect the vitamin and exhibit suitable rheological properties for an effective skin application. In this work, we explored the amphiphilic polymer cholesterol-functionalized polyacrylic acid (PAAbCH) as a stabilizer for oil-in-water emulsions containing vitamin D-3 dissolved in medium-chain triglycerides of coconut oil. Using a semi-industrial mixing process, we prepared emulsions with different ratios of polymer and oil, from 10 to 40% (v/v) and evaluated their droplet size distribution and accelerated physical stability. Emulsions containing 20% (v/v) vitamin D-3 oil exhibited unimodal droplet size distributions with median diameters (D50) in the 4-7 mu m and 10-13 mu m ranges for 0.5% (w/v) and 0.25% (w/v) PAAbCH, respectively, with an extremely low instability index (similar to 0.001) under accelerated centrifugation at 2300g, corresponding to a predicted stability of one year. Moreover, rheological analyses revealed pronounced shearthinning behavior and stable viscoelastic properties, with storage moduli (G ') exceeding loss moduli (G '') in the range 10-10(2) Pa at low frequencies for formulations containing 0.5% PAAbCH, indicative of a well-structured internal network. In vitro skin permeation studies demonstrated that PAAbCH-based emulsions significantly reduced the formation of vitamin D-3 oxidation byproducts during skin exposure, highlighting a protective effect of the polymer matrix. Overall, PAAbCH emerges as a promising multifunctional excipient, enabling the development of stable, scalable, and skin-friendly emulsions with vitamin D-3. These findings open the way for alternative topical or transdermal delivery strategies that could bypass the limitations of oral supplementation.