Due to a broad spectrum of anticancer potential, quercetin (Qu) has attracted substantial attention from various studies. However, its biological application is hindered by poor water solubility and low bioavailability, which limit its therapeutic effectiveness. Amorphous solid dispersion (ASD) technology has emerged as an effective formulation strategy to overcome these limitations by converting crystalline drugs into a high-energy amorphous state and improving molecular dispersion within suitable polymeric carriers. To develop and characterise ASDs of Qu for enhanced anticancer properties. ASDs of Qu were developed using PVP K30 at varying weight ratios, (Qu:PVP): ASD1 (1:9), ASD2 (1:4), and ASD3 (1:2.3). The amorphous nature, molecular interactions, thermal stability, and relaxation dynamics of ASDs were characterised using scanning electron microscope (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and broadband dielectric spectroscopy (BDS). The biological efficacy of the optimized formulation is assessed through antiproliferative studies using breast cancer cell lines, MDA-MB-231 and MCF-7 cell lines. SEM images showed the transformation of crystalline Qu into amorphous structures in the prepared ASDs, while Qu remained visible in the physical mixture. XRD showed amorphization of Qu in ASD1 and ASD2, identifying 1:9 and 1:4 ratios as optimal. However, ASD2 exhibited a mild tendency toward recrystallization. Pure Qu showed poor solubility (0.53 μM in water, 17.32 μM in ethanol), whereas ASDs significantly improved it (22.81–25.83 μM in water, 50.13–99.24 μM in ethanol). TGA showed Qu degradation at 375 K with major decomposition at 620 K (52% residue), whereas ASD1 degraded at 526.5 K and 820 K with 38.41% residue, indicating enhanced stability. DSC showed ASD1’s glass transition at 395 K. BDS revealed a primary relaxation following VFT behaviour ( T g ≈ 438 K, fragility index 116) and a secondary Arrhenius-type relaxation (activation energy 49.5 kJ/mol). ASD1 demonstrated significantly enhanced antioxidant and anti-inflammatory activities compared to pure quercetin in water. In the DPPH assay (2–10 µM), ASD1 in water showed 24% inhibition at 10 µM, compared with 3% for Qu in water, whereas Qu in DMSO reached 65%. In the superoxide scavenging assay (20–100 µM), ASD1 achieved 37% inhibition at 100 µM compared to 10% for Qu in water (58% in DMSO). Similarly, in the nitric oxide scavenging assay, ASD1 exhibited 28% inhibition at 100 µM, whereas Qu in water showed only 1.2% (51% in DMSO), confirming markedly improved bioactivity due to enhanced solubility and molecular dispersion. Cytotoxicity studies demonstrated that ASD1 exhibited lower IC₅₀ values in ethanol against MDA-MB-231 (47.84 ± 0.55 μM vs 73.11 ± 3.4 μM for Qu) and MCF-7 (35.72 ± 0.55 μM vs 48.01 ± 1.28 μM for Qu), confirming its enhanced efficacy over pure quercetin. The results suggest that PVP K30-based ASDs effectively enhance the physicochemical and biological properties of Qu. The increased solubility and thermal stability of ASD1 contributed to its superior antiproliferative activity against TNBC cells. The intermediate fragility index observed by BDS supports its physical stability. Overall, ASD1, with the optimum drug-to-polymer ratio (1:9), shows strong potential as a formulation strategy to overcome Qu’s biopharmaceutical limitations in cancer therapy. The development of ASDs of Qu with PVP K30 significantly enhanced its solubility, thermal stability, and antiproliferative activity. These results support the potential of amorphous dispersion as a viable strategy to improve the therapeutic utility of poorly soluble anticancer compounds like Qu in breast cancer management.
Anu et al. (Sun,) studied this question.