Development and characterization of palbociclib-loaded PLGA nanobubbles for targeted cancer therapy

• Published in: Annales pharmaceutiques françaises
• Main Authors: Kumar, Boddu Kishore, Kumar, Gubbiyappa Shiva
• Format: Journal Article
• Language: English
• Published: France 11.09.2024
• Subjects: Encapsulation efficiency; Targeted drug delivery; Administration ciblée de medicaments; Palbociclib; Cytotoxicity; Cytotoxicité; Efficacité d’encapsulation; Libération déclenchée par ultrasons; Ultrasound-triggered release; Nanobulles PLGA; PLGA nanobubbles
• ISSN: 0003-4509
• DOI: 10.1016/j.pharma.2024.09.005

The objective of this study was to develop and optimize palbociclib-loaded nanobubbles for targeted breast cancer therapy. Biocompatible poly(DL-lactide-co-glycolide) was used to create nanobubbles loaded with palbociclib. The formulation process was meticulously crafted using a three-level Box-Behnken design and a double emulsion solvent evaporation method to precisely tailor the nanobubbles' properties. The Derringer's desirability method optimized variables by transforming responses into a desirability scale, resulting in a global desirability value. Optimal settings, A: 526.97mg, B: 250mg,C: 2.0% w/v, D: 6101rpm, achieved a D value of 0.949. Palbociclib nanobubbles demonstrated a smaller particle size (31.78±2.12) than plain nanobubbles (38.56±3.56). PDI values indicated a uniform size distribution. The zeta potential remained consistent, with values of -31.34±3.36 for plain and -31.56±3.12 for drug-loaded nanobubbles. Encapsulation efficiency was 70.12%, highlighting effective drug encapsulation. Palbociclib release was significantly higher from nanobubbles in pH 7.4, especially with ultrasound, releasing almost 99.34% of the drug. Hemolytic activity assays confirmed safety for injection. Fluorescent intensity analysis revealed a two-fold increase in cellular uptake of palbociclib facilitated by ultrasound. The MTT assay demonstrated enhanced cytotoxicity of palbociclib-loaded nanobubbles, especially with ultrasound, emphasizing their potential for improved therapeutic efficacy. The IC values for palbociclib, without ultrasound, and with ultrasound were 98.3μM, 72.34μM, and 61.34μM, respectively. The significant findings of this study emphasize the potential of palbociclib-loaded nanobubbles as a promising therapeutic system for improved breast cancer treatment.