Optimizing PLGA Nanobubbles For Triggered Enzalutamide Delivery: Preparation, Characterization, And Evaluation Using Design Of Experiments

Enzalutamide (ENZ) serves as an androgen receptor signaling inhibitor, is used to treat prostate cancer, and has received approval from the US FDA. ENZ pharmaceutical applications are hindered due to low solubility, first-pass metabolism, and limited bioavailability. This research aimed to develop and optimize polylactic acid co-glycolic acid (PLGA) nanobubbles as a sustained delivery system for ENZ, improving stability and bioavailability. Through a three-factor, three-level Box Behnken Design, 17 experimental runs were carried out to optimize drug-PLGA nanobubbles. The optimized formulation consisted of a 40 mg drug, 250 mg PLGA, and 1.9% w/v polyvinyl alcohol (PVA)as a stabilizer. The nanobubbles displayed a particle size of 193.5 ± 2.8 nm, polydispersity index of 0.26 ± 0.016, and zeta potential of 31.4 ± 1.17 mV, with an entrapment efficiency of 65.12 ± 2.54%.Analysis through Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed no drug-polymer interaction while scanning electron microscopy revealed uniform spherical nanoparticles. In vitro studies exhibited excellent drug release, and stability studies showed no significant changes after one month. In vivo studies in rats demonstrated increased Cmax (6.84) and AUC0-t (5.874), indicating improved sustained release and absorption. The findings highlight the potential of ENZ-loaded PLGA nanobubbles to enhance drug kinetics and bioavailability, opening possibilities for precise delivery and improved therapeutic effectiveness. This study provides valuable insights into the variables that impact oral absorption in nanobubble formulations, which can inform future strategies for developing oral drugs.