NARENDRA KUNDAVARAPU, KANNADASAN MAHALINGAM, KİRAN KUMAR YADA
Turkish Journal of Pharmaceutical Sciences - 2025;22(4):246-260
Objectives Bortezomib (BTZ) functions as an androgen receptor signalling inhibitor, is used for the treatment of prostate cancer, and has been sanctioned by the United States Food and Drug Administration. The medicinal applications of BTZ are impeded by low solubility, first-pass metabolism, and restricted bioavailability. This study aimed to develop and enhance polylactic acid-co-glycolic acid (PLGA) nanobubbles (NBs) as a sustained-release mechanism for BTZ, thereby augmenting stability and bioavailability. Materials and Methods Seventeen experimental runs were conducted to optimize drug-PLGA NBs using a three-factor, three-level Box-Behnken Design. The improved formulation comprised 30 mg of medication, 250 mg of PLGA, and 2.0% w/v polyvinyl alcohol as a stabilizing agent. RESULTS The NBs exhibited a particle size of 186.9±13.9 nm, a polydispersity index of 0.146±0.042, and a zeta potential of -21.4±2.28 mV, along with an entrapment efficiency of 66.12±1.48%. Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction analysis verified the absence of drug-polymer interactions, whereas scanning electron microscopy demonstrated uniform spherical nanoparticles. In vitro experiments demonstrated superior drug release, and stability assessments indicated no major alterations after one month. Pharmacokinetic studies in rats demonstrated an elevated Cmax (1.69) and area under the curve from time 0 to t (1.63), signifying enhanced sustained release and absorption. The results underscore the capability of BTZ-loaded PLGA NBs to augment drug kinetics and bioavailability, hence facilitating targeted distribution and enhanced therapeutic efficacy. CONCLUSION This investigation offered significant insights into the factors influencing oral absorption in NB formulations, which can guide future methods for oral medication development. BTZ-loaded PLGA nanobubbles showed promising results by enhancing oral absorption and improving pharmacokinetics in the study, which points to their potential use in sustained-release drug delivery. These findings offer a stepping stone toward nanomedicine via the oral route in future drug development.
