Biodegradable nano-architectural PEGylated approach for the improved stability and anticancer efficacy of...

Area of Science:

• Nanotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Bendamustine is a key treatment for Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL).
• Bendamustine's inherent instability hinders effective drug formulation and delivery.
• Developing stable and effective drug delivery systems is crucial for cancer therapy.

Purpose of the Study:

• To enhance bendamustine stability and efficacy using a co-polymeric PEG-PLGA nanoparticulate system.
• To characterize the synthesized PEG-PLGA conjugate and bendamustine-loaded nanoparticles.
• To evaluate the in vitro release, toxicity, and anticancer activity of the developed nanoparticles.

Main Methods:

• Synthesis and characterization of PEG-PLGA co-polymeric conjugate using FT-IR and 1H NMR.
• Preparation and optimization of bendamustine-loaded nanoparticles (PLGA and PEG-PLGA).
• Characterization of nanoparticles (size, zeta potential, SEM, TEM) and in vitro drug release studies.
• Ex vivo hemolytic toxicity and in vitro cytotoxicity assays against cancer cell lines.

Main Results:

• PEG-PLGA nanoparticles (PPBNP 15) showed optimal characteristics: size 297.3±2.055nm, PDI 0.256±0.012, zeta potential -6.62±0.081mV, and entrapment efficiency 52.30±3.66%.
• In vitro studies demonstrated sustained drug release, best fitted by the Krosmeyer-Peppas model.
• PPBNP 15 exhibited significantly reduced hemolytic toxicity (approx. 11%) and enhanced cytotoxicity against MCF-7, T47D, and PC-3 cancer cells compared to free bendamustine.

Conclusions:

• The developed biodegradable PEG-PLGA nanoparticles significantly improve bendamustine's stability and therapeutic potential.
• The nanoparticle formulation demonstrates reduced toxicity and superior anticancer efficacy.
• This approach offers a promising strategy for improved bendamustine-based cancer treatment.