Utilizing Inverse Emulsion Polymerization to Generate Responsive Nanogels for Cytosolic Protein Delivery
| Autor: | Scott J. Eron, Francesca Anson, Sankaran Thayumanavan, Jeanne A. Hardy, Kishore Raghupathi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Pharmaceutical Science
Emulsion polymerization Nanotechnology 02 engineering and technology 010402 general chemistry 01 natural sciences Article Polymerization Synthetic drugs Cytosol Nanocapsules Drug Discovery Humans Biological Products Drug Carriers Delivery vehicle Chemistry Caspase 3 021001 nanoscience & nanotechnology Small molecule Glutathione 0104 chemical sciences Dithiothreitol Systemic administration Molecular Medicine Emulsions 0210 nano-technology Gels Oxidation-Reduction Nanogel Clearance HeLa Cells |
| Popis: | Therapeutic biologics have various advantages over synthetic drugs in terms of selectivity, their catalytic nature, and, thus, therapeutic efficacy. These properties offer the potential for more effective treatments that may also overcome the undesirable side effects observed due to off-target toxicities of small molecule drugs. Unfortunately, systemic administration of biologics is challenging due to cellular penetration, renal clearance, and enzymatic degradation difficulties. A delivery vehicle that can overcome these challenges and deliver biologics to specific cellular populations has the potential for significant therapeutic impact. In this work, we describe a redox-responsive nanoparticle platform, which can encapsulate hydrophilic proteins and release them only in the presence of a reducing stimulus. We have formulated these nanoparticles using an inverse emulsion polymerization (IEP) methodology, yielding inverse nanoemulsions, or nanogels. We have demonstrated our ability to overcome the liabilities that contribute to activity loss by delivering a highly challenging cargo, functionally active caspase-3, a cysteine protease susceptible to oxidative and self-proteolytic insults, to the cytosol of HeLa cells by encapsulation inside a redox-responsive nanogel. |
| Databáze: | OpenAIRE |
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