Amphiphilic Block Copolymers Bearing Ortho Ester Side-Chains: pH-Dependent Hydrolysis and Self-Assembly in Water

• Published in: Macromolecular bioscience 2010-02, Vol.10 (2), p.192-201
• Main Authors: Tang, Rupei, Ji, Weihang, Wang, Chun
• Format: Article
• Language: English
• Subjects: Acrylamides - chemistry; Acrylamides - toxicity; Animals; Applied sciences; Biological and medical sciences; block copolymers; Cell Death - drug effects; drug delivery; Drug Delivery Systems; Esters - chemistry; Exact sciences and technology; General pharmacology; Hydrogen-Ion Concentration - drug effects; Hydrolysis - drug effects; Kinetics; Light; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Molecular Weight; nanoparticles; Nanoparticles - toxicity; Nanoparticles - ultrastructure; NIH 3T3 Cells; Organic polymers; ortho ester; Particle Size; pH responsive; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyethylene Glycols - chemistry; Polyethylene Glycols - toxicity; Polymers - chemistry; Polymers - toxicity; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Scattering, Radiation; Spectrometry, Fluorescence; Time Factors; Water - chemistry
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.200900229

A new type of pH‐responsive block copolymer nanoparticle has been synthesized and characterized. The amphiphilic diblock copolymer, PEG‐b‐PMYM, contains acid‐labile ortho ester side‐chains in the hydrophobic block and can self‐assemble into micelle‐like nanoparticles in water at neutral pH. Hydrolysis of the ortho ester side‐chains follows a distinct exocyclic mechanism and shows pH‐dependent kinetics, which triggers changes in nanoparticle size and morphology. The nanoparticles have been found to be non‐toxic to cells in vitro. The ability to tune the size and morphology of biocompatible block copolymer nanoparticles by controlling the pH‐sensitive side‐chain hydrolysis represents a unique approach that may be exploited to improve the efficacy of nanometer‐scale drug delivery. The well‐defined mechanism and kinetics of the side‐chain hydrolysis at mildly acidic pH causes distinct changes in the size and morphology of a new type of pH‐responsive block copolymer nanoparticle that contains acid‐labile ortho ester side‐chains in the hydrophobic block. Such “smart” polymer nanoparticles may be useful in controlled drug delivery applications where pH‐actuated action is needed.