<b>Optimization and Enhancement of Oral Bioavailability of Dabrafenib as Nanobubbles Using Quality by Design Approach</b>

Background: The use of Poly (lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) aimed at functioning as a delivery system that encounter solubility issues for drugs like dabrafenib (DBF), which belonged to the Biopharmaceutical Classification System (BCS) class II category. These specially designed nanobubbles enhanced the drug’s solubility, stability, and bioavailability, thus improving the therapeutic effectiveness. Moreover, they offered controlled release characteristics and can potentially enhance drug delivery to tissues or cells, maximizing pharmacological results while reducing adverse effects. Methods: PLGA NBs were formulated using solvent evaporation and optimized using a Box Behnken design considering process and formulation parameters. The NBs characterization includes particle size, drug loading, entrapment efficiency, in-vitro studies, haemolytic studies, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimeter (DSC), stability studies, and as well as in-vivo studies in rats. Results: The optimized nanobubbles (NBs) displayed a particle size (PS) of 190.6 ± 18.4 nm, zeta potential of -21 ± 4.2 mV, and polydispersity index (PDI) of 0.397 ± 0.096. With 87.21 ± 3.8% of entrapment efficiency (EE) and 26.29 ± 4.01% drug loading, in-vitro studies revealed a superior drug release (99%) with ultrasound versus plain drugs (20%). FTIR and DSC studies confirmed no drug-polymer interaction. Scanning Electron Microscopy (SEM) images displayed uniform spherical nanosized particles. Haemolytic activity demonstrated safety, and stability studies indicated no significant changes after 30 days. The nanobubbles exhibited increased Cmax (4.74) and AUC0-t (6.82), thereby promising an enhanced solubility, absorption, and extended half-life. Conclusion: The current investigation showed that PLGA nanobubbles loaded with dabrafenib have a promising delayed release potential, which might make them a possible treatment alternative for breast cancer.