DEVELOPMENT AND OPTIMIZATION OF SOLID LIPID NANOPARTICLES OF DASATINIB USING DESIGN OF EXPERIMENTS: IN VITRO DRUGRELEASE AND IN-VIVO PHARMACOKINETIC STUDIES

Chandu Vamshi Gangula; Seema Tomar; Poli Reddy Papagatla

Authors

Chandu Vamshi Gangula *Research Scholar, Faculty of Pharmaceutical Sciences, Motherhood University, Dehradun Road, Karoundi Village, Bhagwanpur post, Roorkee Tehsil, Haridwar Distt., Uttarakhand, India 247661. Author
Seema Tomar Professor, Faculty of Pharmaceutical Sciences, Motherhood University, Dehradun Road, Karoundi Village, Bhagwanpur post, Roorkee Tehsil, Haridwar Distt., Uttarakhand, India 247661. Author
Poli Reddy Papagatla Professor, Nalanda College Of Pharmacy, Nalgonda, Telangana, India. Author

Keywords:

Dasatinib, Nanoparticles, Stearic acid, Design of experiments, In vivo pharmacokinetics

Abstract

Dasatinib, a potent BCR-ABL tyrosine kinase inhibitor, suffers from poor aqueous solubility and pHdependent absorption, leading to variable bioavailability and frequent dosing in leukemia therapy. Solid lipid
nanoparticles (SLNs) offer a promising strategy to enhance solubility, prolong release, and improve systemic
exposure. This study developed and optimized Dasatinib-loaded SLNs using a Box-Behnken design to
systematically evaluate the effects of lipid weight (500–1000 mg), surfactant concentration (0.5–2% w/v),
and homogenization time (4–10 min) on critical quality attributes. The optimized SLNs (900 mg lipid, 1.75%
surfactant, 8.5 min homogenization) exhibited a particle size of 204 nm, zeta potential of -27.3 mV, and
entrapment efficiency of 85.8%, closely matching predicted values (R² > 0.94). FTIR and DSC confirmed
successful drug encapsulation within the lipid matrix, while SEM revealed spherical, monodisperse
nanoparticles. In vitro release studies demonstrated sustained drug release (95% at 24 h) following the
Korsmeyer-Peppas model (R² = 0.995, n = 0.56), indicating combined diffusion-erosion mechanisms. In
vivo pharmacokinetics in rats showed a 1.6-fold increase in AUC and prolonged Tmax (8 h vs. 2 h for pure
drug), confirming enhanced bioavailability. These results highlight the potential of SLNs to overcome
Dasatinib’s delivery challenges, offering a scalable nanocarrier system for improved leukemia treatment.

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