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

Boddu Kishore Kumar; Gubbiyappa Shiva Kumar

doi:10.1016/j.pharma.2024.09.005

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

Ann Pharm Fr. 2024 Sep 11:S0003-4509(24)00138-X. doi: 10.1016/j.pharma.2024.09.005. Online ahead of print.

Authors

Boddu Kishore Kumar¹, Gubbiyappa Shiva Kumar²

Affiliations

¹ GITAM School of Pharmacy, GITAM Deemed to be University, 502329 Hyderabad, Telangana, India.
² GITAM School of Pharmacy, GITAM Deemed to be University, 502329 Hyderabad, Telangana, India. Electronic address: shivakumar.gubbiyappa@gitam.edu.

PMID: 39270837
DOI: 10.1016/j.pharma.2024.09.005

Abstract

Objective: The objective of this study was to develop and optimize palbociclib-loaded nanobubbles for targeted breast cancer therapy.

Materials and methods: 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.

Results: 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 IC₅₀ values for palbociclib, without ultrasound, and with ultrasound were 98.3μM, 72.34μM, and 61.34μM, respectively.

Conclusion: The significant findings of this study emphasize the potential of palbociclib-loaded nanobubbles as a promising therapeutic system for improved breast cancer treatment.

Keywords: Administration ciblée de medicaments; Cytotoxicity; Cytotoxicité; Efficacité d’encapsulation; Encapsulation efficiency; Libération déclenchée par ultrasons; Nanobulles PLGA; PLGA nanobubbles; Palbociclib; Targeted drug delivery; Ultrasound-triggered release.