Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives

This paper presents a review of living radical polymerization achieved with thiocarbonylthio compounds [ZC(=S)SR] by a mechanism of reversible addition–fragmentation chain transfer (RAFT). Since we first introduced the technique in 1998, the number of papers and patents on the RAFT process has increased exponentially as the technique has proved to be one of the most versatile for the provision of polymers of well defined architecture. The factors influencing the effectiveness of RAFT agents and outcome of RAFT polymerization are detailed. With this insight, guidelines are presented on how to conduct RAFT and choose RAFT agents to achieve particular structures. A survey is provided of the current scope and applications of the RAFT process in the synthesis of well defined homo-, gradient, diblock, triblock, and star polymers, as well as more complex architectures including microgels and polymer brushes.

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Living radical polymerization by the RAFT process

http://wwwcourses.sens.buffalo.edu/ce435/Riess03.pdf

Micellization of block copolymers

In recent years, zwitterionic materials such as poly(carboxybetaine) (pCB) and poly(sulfobetaine) (pSB) have been applied to a broad range of biomedical and engineering materials. Due to electrostatically induced hydration, surfaces coated with zwitterionic groups are highly resistant to nonspecific protein adsorption, bacterial adhesion, and biofilm formation. Among zwitterionic materials, pCB is unique due to its abundant functional groups for the convenient immobilization of biomolecules. pCB can also be prepared in a hydrolyzable form as cationic pCB esters, which can kill bacteria or condense DNA. The hydrolysis of cationic pCB esters into nonfouling zwitterionic groups will lead to the release of killed microbes or the irreversible unpackaging of DNA. Furthermore, mixed-charge materials have been shown to be equivalent to zwitterionic materials in resisting nonspecific protein adsorption when they are uniformly mixed at the molecular scale.

Ultralow-Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications

This paper provides a third update to the review of reversible deactivation radical polymerization (RDRP) achieved with thiocarbonylthio compounds (ZC(=S)SR) by a mechanism of reversible addition-fragmentation chain transfer (RAFT) that was published in June 2005 (Aust. J. Chem. 2005, 58, 379). The first update was published in November 2006 (Aust. J. Chem. 2006, 59, 669) and the second in December 2009 (Aust. J. Chem. 2009, 62, 1402). This review cites over 700 publications that appeared during the period mid 2009 to early 2012 covering various aspects of RAFT polymerization which include reagent synthesis and properties, kinetics and mechanism of polymerization, novel polymer syntheses, and a diverse range of applications. This period has witnessed further significant developments, particularly in the areas of novel RAFT agents, techniques for end-group transformation, the production of micro/nanoparticles and modified surfaces, and biopolymer conjugates both for therapeutic and diagnostic applications.

/pdf/living-radical-polymerization-by-the-raft-process-a-second-3rre2ur7xt.pdf

Living Radical Polymerization by the RAFT Process - A Second Update

Synthesis and solution properties of zwitterionic polymers.

Homopolymers of sodium 4-styrenesulfonate have been synthesized directly in aqueous media by reversible addition−fragmentation chain transfer polymerization (RAFT). The resulting homopolymers have narrow molecular weight distributions, with polydispersity indices in the range 1.12−1.25, as determined by aqueous size exclusion chromatography. Using a dithioester-capped sodium 4-styrenesulfonate homopolymer as a macro chain transfer agent, a block copolymer with sodium 4-vinylbenzoate has been prepared in aqueous media. Additionally, a block copolymer of (ar-vinylbenzyl)trimethylammonium chloride with N,N-dimethylvinylbenzylamine has been synthesized, using the same methodology. We believe these represent the first examples of AB diblock copolymers prepared directly in aqueous media via the RAFT process. Both block copolymers are stimuli-responsive and undergo reversible pH-induced micellization in aqueous solution. Micelles with hydrodynamic diameters in the range 18−38 nm were observed by dynamic light sc...

Water-Soluble Polymers. 81. Direct Synthesis of Hydrophilic Styrenic-Based Homopolymers and Block Copolymers in Aqueous Solution via RAFT

We report aqueous, room temperature RAFT polymerization of N-isopropylacrylamide (NIPAM) and, subsequently, its block copolymerization utilizing a poly(N,N-dimethylacrylamide) macro-CTA. A series of thermally responsive AB diblock and ABA triblock copolymers have been prepared. These polymers contain hydrophilic N,N-dimethylacrylamide (DMA) A blocks of fixed molecular weight and temperature-responsive NIPAM B blocks of varied chain length. Using a combination of 1H NMR spectroscopy, T2 relaxation measurements, dynamic light scattering (DLS), and static light scattering (SLS), we demonstrate that these block copolymers are indeed capable of reversibly forming micelles in response to changes in solution temperature and that the micellar size and transition temperature are dependent on both the NIPAM block length and the polymer architecture (diblock vs triblock).

Direct Synthesis of Thermally Responsive DMA/NIPAM Diblock and DMA/NIPAM/DMA Triblock Copolymers via Aqueous, Room Temperature RAFT Polymerization†

Facile, controlled, room-temperature RAFT polymerization of N-isopropylacrylamide.

The controlled radical polymerization (CRP) technique reversible addition−fragmentation chain transfer (RAFT) has potential for preparing functional (co)polymers directly in an aqueous environment. Hydrolysis and aminolysis can eliminate the active end groups necessary for maintaining “livingness” in water. These reactions have not previously been evaluated with respect to their effect on aqueous RAFT polymerizations. Herein we determine rate constants of hydrolysis and aminolysis for representative water-soluble chain transfer agents (CTAs) cyanopentanoic acid dithiobenzoate (CTP) and the macro-chain-transfer agents (macro-CTAs) of poly(sodium 2-acrylamido-2-methylpropanesulfonate) (AMPSX) and poly(acrylamide) (AMX) at selected pH values. Rates of hydrolysis and aminolysis both increase with increasing pH and decrease with increasing molecular weight of the dithioester. On the basis of these rate constants, mathematical relationships have been developed to predict the number of living chain ends and the ...

and Andrew B. Lowe

Papers

Synthesis and solution properties of zwitterionic polymers.

Water-Soluble Polymers. 81. Direct Synthesis of Hydrophilic Styrenic-Based Homopolymers and Block Copolymers in Aqueous Solution via RAFT

Direct Synthesis of Thermally Responsive DMA/NIPAM Diblock and DMA/NIPAM/DMA Triblock Copolymers via Aqueous, Room Temperature RAFT Polymerization†

Facile, controlled, room-temperature RAFT polymerization of N-isopropylacrylamide.

Hydrolytic Susceptibility of Dithioester Chain Transfer Agents and Implications in Aqueous RAFT Polymerizations