Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend Particles
Xi Zhan1, Kenny K Tran, Liguo Wang
1Department of Biological Structure, University of Washington School of Medicine, Seattle, WA, 98195, USA.
Pharmaceutical Research
|January 17, 2015
Summary
This study developed a novel polymeric particle system for efficient intracellular delivery. The particles successfully deliver cargo into the cell while minimizing the release of harmful enzymes, enhancing safety.
Area of Science:
- Biomaterials Science
- Cell Biology
- Drug Delivery Systems
Background:
- Intracellular delivery of therapeutic agents requires endosomal escape.
- Minimizing digestive enzyme release from endosomes is crucial for cellular function.
Purpose of the Study:
- To investigate a particle delivery platform using blended poly(lactic-co-glycolic acid) (PLGA) and a pH-sensitive copolymer.
- To assess intracellular distribution of fluorescent cargoes and enzymes using this platform.
Main Methods:
- Utilized microscopic and biochemical methods for semi-quantitative assessment.
- Evaluated endosomal escape of various cargo sizes and enzyme release into the cytosol.
Main Results:
- Polymeric particles facilitated controlled cytosolic delivery, primarily dependent on cargo size.
- Particles did not cause endosomal/lysosomal rupture, releasing <20% of enzymes.
Conclusions:
- The blend particles offer a promising platform for intracellular delivery of biologics and drugs.
- This system demonstrates potential for targeted intracellular delivery with minimized cellular toxicity.
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