IntroductionAccording to previous studies, vitamin D3 can be helpful in treating PCOS. However, its low solubility and bioavailability decelerate treatment and increase the required dose. This study aimed to examine the efficacy of PhytoSolve formulation in increasing vitamin D3 solubility and improving PCOS treatment. MethodsThe PhytoSolve formulation contained a mixture of lipid S75, glycerol, and MCT oil, which were prepared using a probe sonicator. In this study, 36 female NMRI mice were allocated to six groups: sham, PCOS model, control, PhytoSolve formulation, vitamin D3-containing PhytoSolve formulation and vitamin D3. DHEA was injected to induce the PCOS model. Vitamin D3 was administered by gavage for one week from day 13, after which serum samples were collected to examine CTRP6 gene and protein expression and determine the serum vitamin D3 concentration. ResultsThe mean particle size in the PhytoSolve formulation was 71.10 ± 1.100 nm; after 120 h, the release rate of vitamin D3 from the PhytoSolve formulation was 91.5%. Based on the results, the CTRP6 gene and protein expression were significantly reduced in the VD3-containing PhytoSolve group compared to the vitamin D3 group (P < 0.05). ConclusionBased on the present findings, vitamin D3 loaded in the PhytoSolve formulation was more effective in the treatment of PCOS compared to its suspension form. Therefore, is suggested to use the PhytoSolve formulation as an effective delivery system for drugs with low solubility and bioavailability.