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Controlled drug release from polyelectrolyte-drug conjugate nanoparticles
Ruginn Catarata1, Nilab Azim2, Santanu Bhattacharya3
1NanoScience Technology Center, University of Central Florida, Orlando, Florida 32826, USA. lzhai@ucf.edu.
Journal of Materials Chemistry. B
|March 20, 2020
Summary
This study developed poly(acrylic acid) (PAA)-Gemcitabine (GEM) nanoparticles for controlled anticancer drug release. These nanoparticles effectively deliver GEM to pancreatic cancer cells, showing similar efficacy to free GEM with delayed release.
Area of Science:
- Materials Science
- Nanotechnology
- Drug Delivery
Background:
- Controlled drug release is crucial for effective therapy.
- Hydrophobic anticancer drugs pose challenges for systemic delivery.
- Nanoparticle encapsulation offers a strategy for targeted and sustained drug release.
Purpose of the Study:
- To develop a general method for encapsulating hydrophobic drugs in polyelectrolyte nanoparticles.
- To create poly(acrylic acid) (PAA)-Gemcitabine (GEM) conjugate nanoparticles for controlled release of GEM in pancreatic cancer cells.
- To evaluate the stability, drug loading, release kinetics, and in vitro efficacy of these PAA-GEM nanoparticles.
Main Methods:
- Fabrication of PAA-GEM conjugate nanoparticles via amide bond formation.
- Optimization of PAA/GEM ratio and pH for nanoparticle stability and drug loading.
- Characterization of nanoparticle size, surface charge, encapsulation efficiency, and loading capacity using TEM, DLS, and zeta potential measurements.
- In vitro drug release studies in phosphate-buffered saline (PBS).
- Cytotoxicity assays using PANC-1 human pancreatic cancer cells.
- Cellular uptake studies using rhodamine G6-labeled PAA-GEM nanoparticles.
Main Results:
- Optimized PAA-GEM nanoparticles exhibited a stable core-shell structure with controlled sizes (12-60 nm).
- High encapsulation efficiency (29.29 ± 1.7%) and loading capacity (9.44 ± 0.46%) were achieved.
- Less than 7% GEM was released over 96 hours in PBS, demonstrating sustained release.
- PAA-GEM nanoparticles showed comparable cytotoxic efficacy to free GEM in PANC-1 cells with a significant release delay (>48 hours).
- Rapid cellular uptake of PAA-GEM nanoparticles by PANC-1 cells was observed within 2 hours.
Conclusions:
- PAA-GEM conjugate nanoparticles provide a viable platform for controlled delivery of hydrophobic anticancer drugs like GEM.
- The developed nanoparticles ensure sustained drug release and maintain therapeutic efficacy against pancreatic cancer cells.
- The nanoparticles are efficiently internalized by cancer cells, facilitating intracellular drug release and therapeutic action.
