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<p>The current work proposes a new approach to improve the apparent solubility and oral bioavailability of Pazopanib Hydrochloride (PZB), a solubility-limited tyrosine kinase inhibitor, by surface adsorption within Mesoporous Silica Nanoparticles (MSNs) for oral drug administration. Originality is in utilizing large surface area and tunable mesopores of MSNs to facilitate partial amorphization and controlled release, far beyond the solubility barrier of PZB (0.56 ± ± 0.013&#xa0;µg/mL). PZB was surface adsorbed into MSNs using incipient wetness impregnation, and the F8 optimized batch (3:1 PZB-to-MSN) showed 83.54 ± 2.43 w/w % drug loading and 51.56-fold solubility improvement (28.97 ± 0.79&#xa0;µg/mL). Comprehensive characterization by DLS, SEM, DSC, ATR-IR, and XRD proved successful surface adsorption, structural integrity, and decreased crystallinity, which facilitated improved dissolution. In vitro experiments showed a 2.04-to-2.74-fold improvement in drug release under pH-simulated conditions compared to PZB. Cytotoxicity against renal carcinoma cells (786-O) proved retained or even improved anticancer activity, with 75.5% cell viability at 80&#xa0;µg/mL. Pharmacokinetic assessment in Wistar rats proved a 2.62-fold improvement in C<sub>max</sub> and a 3.45-fold improvement in AUC for PZB-MSN compared to PZB. This MSN-based nano formulation takes advantage of the distinctive pore architecture of MSNs to immobilize PZB molecules, lowering lattice energy and facilitating targeted delivery to tumor tissues. These results present MSNs as an emerging platform to enhance oral bioavailability along with therapeutic efficacy of solubility-limited anticancer drugs such as PZB, with therapeutic efficacy for clinical deployment against renal cell carcinoma.</p> Graphical Abstract <p></p>

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Mesoporous Silica Nanoparticles for Improved Solubility and Bioavailability of Pazopanib in the Treatment of Renal Cell Carcinoma

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Minal Patil,
  • Suprit Saoji,
  • Ashish Gaikwad,
  • Chandragouda Patil,
  • Hitendra Mahajan

摘要

The current work proposes a new approach to improve the apparent solubility and oral bioavailability of Pazopanib Hydrochloride (PZB), a solubility-limited tyrosine kinase inhibitor, by surface adsorption within Mesoporous Silica Nanoparticles (MSNs) for oral drug administration. Originality is in utilizing large surface area and tunable mesopores of MSNs to facilitate partial amorphization and controlled release, far beyond the solubility barrier of PZB (0.56 ± ± 0.013 µg/mL). PZB was surface adsorbed into MSNs using incipient wetness impregnation, and the F8 optimized batch (3:1 PZB-to-MSN) showed 83.54 ± 2.43 w/w % drug loading and 51.56-fold solubility improvement (28.97 ± 0.79 µg/mL). Comprehensive characterization by DLS, SEM, DSC, ATR-IR, and XRD proved successful surface adsorption, structural integrity, and decreased crystallinity, which facilitated improved dissolution. In vitro experiments showed a 2.04-to-2.74-fold improvement in drug release under pH-simulated conditions compared to PZB. Cytotoxicity against renal carcinoma cells (786-O) proved retained or even improved anticancer activity, with 75.5% cell viability at 80 µg/mL. Pharmacokinetic assessment in Wistar rats proved a 2.62-fold improvement in Cmax and a 3.45-fold improvement in AUC for PZB-MSN compared to PZB. This MSN-based nano formulation takes advantage of the distinctive pore architecture of MSNs to immobilize PZB molecules, lowering lattice energy and facilitating targeted delivery to tumor tissues. These results present MSNs as an emerging platform to enhance oral bioavailability along with therapeutic efficacy of solubility-limited anticancer drugs such as PZB, with therapeutic efficacy for clinical deployment against renal cell carcinoma.

Graphical Abstract