PREPARATION AND EVALUATION OF ENTRECTINIB PLGA NANOBUBBLES BY CENTRAL COMPOSITE DESIGN

P. NANDINI; D. V. R. N. BHIKSHAPATHI

doi:10.22159/ijap.2025v17i1.50891

Authors

P. NANDINI BirTikandrajit University, Canchipur, Imphal West-795003, Manipur, India
D. V. R. N. BHIKSHAPATHI BirTikandrajit University, Canchipur, Imphal West-795003, Manipur, India

DOI:

https://doi.org/10.22159/ijap.2025v17i1.50891

Keywords:

Entrectinib, Cancer, Solvent-diffusion-evaporation technique, Central composite design, Nanobubbles, Entrectinib, solvent-diffusion-evaporation technique, central composite design, nanobubbles, ultrasound-assisted medication, cytotoxicity., cytotoxicity

Abstract

Objective: For targeted delivery of entrectinib, we created nanobubbles with a poly(lactic-co-glycolic acid) (PLGA) shell and a perfluoropentane core.

Methods: Entrectinib was encapsulated in PLGA nanobubbles by a modified W/O/W double emulsion, solvent-diffusion-evaporation technique. Central composite design was utilized to explore how four independent factors like sonication distance (X1), amplitude (X2), time (X3), and power (X4)—affected droplet size (Y1) and polydispersity Index (PDI) (Y2).

Results: The optimal sonication distance, time, amplitude, and power were 2.41 cm; 3.61 min, 44.42%, and 77.35 W. Drug-loaded nanobubbles showed a PDI of 0.196±0.005 and an average particle size of 73.53±3.08 nm, indicating a unimodal system with low PDI high zeta potential indicate formulation stability. The mean drug loading capacity was 29.27±1.54 mg/g. The remarkable drug encapsulation efficiency (82.12±2.98%) supports an inclusion complex. Transmission Electron Microscopy shows drug encapsulation does not change nanobubbles' spherical shape. Fourier-transform infrared spectroscopy and Differential scanning calorimetry revealed nanobubble-drug complex production. Nanobubbles emitted more entrectinib than the solution. Drug release via ultrasound was different. At 6 hours, sonication released 46.08% of entrectinib and 26.42% without. Entrectinib released 99.34% after 24 hours versus 58.93% without ultrasonography. The formulation's consistent size distribution remained stable after 180 days. Parenteral safety and non-toxicity were shown by these nanobubbles at 15 mg/ml. In vitro ultrasonic increases cell uptake. The viability of MCF-7 cells was assessed following exposure to entrectinib at 10 to 120 μM dosages. All entrectinib formulations showed little cytotoxicity, up to 98% cell survival at 10 μM doses.

Conclusion: PLGA nanobubbles can be used in ultrasound-responsive formulations to deliver targeted drugs to fight cancer and other diseases.

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