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Purpose <p>Despite its efficacy against chronic myeloid leukemia (CML), dasatinib (DAS) exhibits dose-limiting toxicities and suboptimal pharmacokinetics. This study aimed to develop an optimized liposomal DAS formulation to reduce adverse effects while enhancing therapeutic efficacy.</p> Methods <p>DAS-loaded liposomes were prepared using thin film hydration and optimized through central composite design. The formulation was characterized for physicochemical properties, in vitro release, and in vivo pharmacokinetics in Wistar rats.</p> Results <p>The optimized DAS liposomes demonstrated excellent properties: high entrapment efficiency (95.2 ± 1.8%), nano-sized particles (277.7 ± 4.2&#xa0;nm), narrow size distribution (PDI 0.014 ± 0.001), and appropriate surface charge (-15.1 ± 0.8 mV). Transmission electron microscopy confirmed spherical morphology with bilayer thickness of 27.3 ± 2.1&#xa0;nm. The lyophilized formulation exhibited sustained release (75.59 ± 3.4% over 48&#xa0;h vs. 94.2 ± 2.8% at 8&#xa0;h for free drug). Pharmacokinetic studies revealed significantly enhanced bioavailability (AUC₀₋ₜ of 48.14 ± 2.41 vs. 13.56 ± 0.64 ng·h/mL, <i>p</i> &lt; 0.05), extended half-life (44.58 ± 1.89 vs. 25.82 ± 1.98&#xa0;h, <i>p</i> &lt; 0.05), and delayed Tₘₐₓ (16 ± 1.47 vs. 0.5 ± 0.01&#xa0;h, <i>p</i> &lt; 0.05) compared to free DAS. Notably, the liposomal formulation demonstrated complete elimination of mortality in acute toxicity studies.</p> Conclusion <p>The novel liposomal DAS formulation offers a promising therapeutic approach for CML treatment with enhanced pharmacokinetic profile and substantially reduced toxicity.</p>

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Novel Liposomal Nanocarrier of Dasatinib for Enhanced Chronic Myeloid Leukemia Treatment: Improved Pharmacokinetics and Reduced Toxicity

  • 期刊论文

  • 发表日期：

    2025年10月22日

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  • Rajesh Palva,
  • Francis Lobo,
  • Rajnikant Suthar,
  • Musaratafrin Saiyed

摘要

Purpose

Despite its efficacy against chronic myeloid leukemia (CML), dasatinib (DAS) exhibits dose-limiting toxicities and suboptimal pharmacokinetics. This study aimed to develop an optimized liposomal DAS formulation to reduce adverse effects while enhancing therapeutic efficacy.

Methods

DAS-loaded liposomes were prepared using thin film hydration and optimized through central composite design. The formulation was characterized for physicochemical properties, in vitro release, and in vivo pharmacokinetics in Wistar rats.

Results

The optimized DAS liposomes demonstrated excellent properties: high entrapment efficiency (95.2 ± 1.8%), nano-sized particles (277.7 ± 4.2 nm), narrow size distribution (PDI 0.014 ± 0.001), and appropriate surface charge (-15.1 ± 0.8 mV). Transmission electron microscopy confirmed spherical morphology with bilayer thickness of 27.3 ± 2.1 nm. The lyophilized formulation exhibited sustained release (75.59 ± 3.4% over 48 h vs. 94.2 ± 2.8% at 8 h for free drug). Pharmacokinetic studies revealed significantly enhanced bioavailability (AUC₀₋ₜ of 48.14 ± 2.41 vs. 13.56 ± 0.64 ng·h/mL, p < 0.05), extended half-life (44.58 ± 1.89 vs. 25.82 ± 1.98 h, p < 0.05), and delayed Tₘₐₓ (16 ± 1.47 vs. 0.5 ± 0.01 h, p < 0.05) compared to free DAS. Notably, the liposomal formulation demonstrated complete elimination of mortality in acute toxicity studies.

Conclusion

The novel liposomal DAS formulation offers a promising therapeutic approach for CML treatment with enhanced pharmacokinetic profile and substantially reduced toxicity.