Stimuli‐responsive glycopolymer brushes composed of N‐acryloyl glucosamine (AGA) and N‐isopropylacrylamide (NIPAAm) were prepared using RAFT polymerization. The RAFT agent was immobilized on the ...surface of a treated silicon waver via covalent attachment using the Z‐group. PAGA and PNIPAAm brushes showed a linear increase in brush thickness with the consumption of monomer in solution. The polymers generated in solution confirm the living behavior with the molecular weight increasing linearly with monomer conversion while the molecular weight distribution remains narrow. Additionally, the ability of PAGA brushes to grow further in the presence of NIPAAm reveals the presence of an active RAFT end group indicative of a living system. PAGA and PNIPAAm homopolymer brushes up to 30 nm were grown using this technique. PAGA brushes were utilized for further chain extension to generate stimuli‐responsive brushes with block structures of PAGA and PNIPAAm. The PAGA‐block‐PNIPAAm brushes were found to grow in size with the consumption of NIPAAm. Contact angle measurements confirm the suggested mechanism showing that the second monomer is incorporated between the first layer and the silicon surface as expected using the Z‐group approach.
Structure of the stimuli‐responsive glycopolymer brushes.
Hollow polymeric nanoparticles with a hydrophilic liquid core have been synthesized in a one-pot approach via a novel inverse miniemulsion periphery RAFT polymerization process. Successful ...encapsulation and release of a model protein is reported as a potential application.
Most low molecular weight platinum-based anticancer drugs have a short circulation time in the bloodstream. One of the potential strategies to improve the targeted delivery of cisplatin and prolong ...its circulation is via the use of nanocarriers. An improved drug delivery system was developed via reversible addition-fragmentation chain transfer (RAFT) polymerization. In a one-pot reaction, the incorporation of anticancer drug and core cross-linking was simultaneously carried out by using the highly effective reaction of isocyanate groups in the core of the polymeric micelles poly(oligo(ethylene glycol) methyl ether methacrylate)-block-poly(styrene-co-3-isopropenyl-α,α-dimethylbenzyl isocyanate) (POEGMA-block-P(STY-co-TMI)) with amine groups in the prepared platinum(IV) drug. The micelles with platinum(IV) incorporated with a size of 36 nm were very stable in water. In a reductive environment, in this study simulated using ascorbate, the drug was released at a slow rate of 82% in 22 days and at the same time the cross-linked micelle broke down into free block copolymers as evidenced using inductively coupled plasma-mass spectrometer (ICP-MS), size exclusion chromatography (SEC), and dynamic light scattering (DLS). The in vitro study also revealed the promising antitumor activity of prepared platinum(IV) drugs encapsulated into the micelle structure.
Peptides take on an increasingly important role as therapeutics in areas including diabetes, oncology, and metabolic, cardiovascular, and infectious diseases. In addition, many peptides such as ...insulin have been employed for many years. A challenge in the administration of peptide drugs is their often low hydrolytic stability, as well as other problems that are common to any drug treatment such as systemic distribution. There is a significant attention in the literature of protein drugs and their delivery strategies, but not many overviews are specifically dedicated to peptides. In this review, the different approaches to deliver peptides have been summarized where the focus is only on drug carriers based on organic materials. Initial discussion is on different methods of polymer-peptide conjugation before being followed by physical encapsulation techniques, which is divided into surfactant-based techniques and polymer carriers. Surfactant-based techniques are dominated by liposome, microemulsions and solid-lipid nanoparticles. The field widens further in the polymer field. The delivery of peptides has been enhanced using polymer-decorated liposomes, solid microspheres, polyelectrolyte complex, emulsions, hydrogels, and injectable polymers. The aim of this article is to give the reader an overview over the different types of carriers.
Well-defined linear poly(acryloyl glucosamine) (PAGA) exhibiting molar masses ranging from 3 to 120 K and low polydispersities have been prepared via reversible addition-fragmentation chain transfer ...polymerization (RAFT) in aqueous solution without recourse to protecting group chemistry. The livingness of the process was further demonstrated by successfully chain-extending one of these polymers with N-isopropylacrylamide affording narrow dispersed thermosensitive diblocks. This strategy of polymerization was finally extended to the preparation of glycopolymer stars from Z designed non-water-soluble trifunctional RAFT agent. After the growth of very short blocks of poly(hydroxyethyl acrylate) ((-)DP(n)(branch) = 10), AGA was polymerized in aqueous solution in a controlled manner affording well-defined 3-arm glycopolymer stars.
Eight xanthates were synthesized to induce living free radical polymerization of vinyl acetate. Four compounds, methyl (4‐methoxyphenoxy)carbonothioylsulfanyl acetate, methyl ...(methoxycarbonothioyl)sulfanyl acetate, methyl (ethoxycarbonothioyl)sulfanyl acetate and methyl (isopropoxycarbonothioyl)sulfanyl acetate were identified as suitable MADIX/RAFT agents, yielding low polydispersity (PDI < 1.2) poly(vinyl acetate) of molecular weights exceeding 5 × 104 g · mol−1. All suitable MADIX/RAFT agents exhibited extended periods of inhibition (0.3 h < tinh < 10 h) and moderate rate retardation. The ability of these compounds to control vinyl acetate polymerization can be correlated with the electron density on the central carbon atom of the xanthate. Electrospray ionization mass spectrometric analysis was performed to complete the investigation on the new MADIX/RAFT agents.
The synthesis of polystyrene-block-poly(N,N-dimethylacrylamide) (PS-b-PDMA) via RAFT polymerization was investigated in detail. Two different RAFT agents – benzyl dithiobenzoate and ...3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, were employed to prepare polystyrene macroRAFT agents with molecular weights varying between 3000gmol−1 and 62,000gmol−1 and polydispersities between 1.1 and 1.4. Chain extensions with N,N-dimethylacrylamide (DMA) were carried out using a constant monomer to RAFT agent concentration (DMA/RAFT=500), to compare the rate of polymerization in dependency of the polystyrene chain length. A decreasing rate of polymerization with increasing block length was observed. Depending on the sizes of the first block and type of RAFT agents used, chain extension polymerization with DMA was found to be incomplete, leading to significant low molecular weight tailing in the GPC analyses. Block copolymers prepared using 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, followed the expected molecular weight evolutions with polydispersity indices of 1.2–1.4. In contrast, block copolymers using benzyl dithiobenzoate clearly showed bimodal molecular weight distributions, especially when the longest PS macroRAFT agent with a molecular weight of 38,000gmol−1 was employed. These amphiphilic block copolymers were used to fabricate honeycomb structured porous films using the breath figure technique. The regularity of the film was considerably influenced by the humidity of the environment, which could be controlled by the rate of the airflow or the humidity in the casting chamber. The interaction between the hydrophilic block copolymer and the humidity was found responsible for the delicate equilibrium during the casting process, which prevented high pores regularity at very low (below 50%) and at elevated (above 80%) humidity. The interactions of the hydrophilic block with the humidity were observed to superimpose an additional nano-scaled order onto the hexagonal micron-sized porous array. Pores, which are created by encapsulation of water droplets, were found to be more hydrophilic than the surface. Confocal microscopy studies were employed to locate hydrophilic blocks within the film using a fluorescence labeled PDMA polymer.
The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N‐(2‐hydroxypropyl)methacrylamide (HPMA) and Boc protected ...1,3‐diaminopropan‐2‐yl acrylate (Ac‐DAP‐Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition‐fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA14‐co‐(Ac‐DAP‐Boc)9) and a molecular weight of Mn = 7600 g mol−1 (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI–TOF (matrix assisted laser desorption ionization time‐of‐flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer–albumin conjugates self‐assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.
Delivery of platinum drugs using macromolecular platinum complexes is already an established pathway. Conjugation of these macromolecular drugs to albumin results in the formation of core–shell nanoparticles. As a result, the delivery of these drugs into ovarian cancer cells is enhanced leading to significantly higher drug activity.
The alignment of anisotropic nanoparticles in flow has been used for a range of applications such as the preparation of strong fibres and the assembly of in‐plane aligned 1D‐nanoobjects that are used ...for electronic devices, sensors, energy and biological application. Important is also the flow behaviour of nanoparticles that were designed for nanomedical applications such as drug delivery. It is widely observed that non‐spherical nanoparticles have longer circulation times and a more favourable biodistribution. To be able to understand this behaviour, researchers have turned to analyzing the flow of non‐spherical nanoparticles in the blood stream. In this review, an overview of microfluidic techniques that are used to monitor the alignment of anisotropic nanoparticles in solution will be provided, which includes analysis by small angle X‐ray scattering (SAXS) and polarized light microscopy. The flow of these nanoparticles in blood is then discussed as the presence of red blood cells causes margination of some nanoparticles. Using fluorescence microscopy, the extent of margination can be identified, which coincides with the ability of nanoparticles to adhere to the cells grown along the wall. While these studies are mainly carried out in vitro using blood, initial investigations in vivo were able to confirm the unusual flow of anisotropic nanoparticles.
There is an increased interest in the use of non‐spherical nanoparticles for drug delivery as they often display better blood circulation time. However, there is little understanding of the behaviour of these nanoparticles in blood flow. Microfluidic devices can now gain better insight as alignment of anisotropic nanoparticles as well as their margination towards the blood vessel wall can be directly observed .
The coupling of the reversible addition fragmentation chain transfer (RAFT) polymerization technique with the copper-catalyzed Huisgen 1,3-dipolar cycloaddition (“click chemistry”) as a simple and ...effective way to generate polystyrene (PS) macrocycles is presented. The novel strategy entails the synthesis of linear PS backbones followed by endgroup modification to facilitate click chemistry for the formation of ring shaped polymers. An azido group modified 4-cyanopentanoic acid dithiobenzoate is employed as the chain transfer agent in the RAFT mediated polymerization of styrene to form PS with Mn from 2000gmol−1 to 6000gmol−1 and PDI<1.2. To facilitate the cyclization of the polystyrene chains by click coupling, the thiocarbonylthio endgroup is removed and concomitantly replaced by an alkyne bearing function. This is carried out via the radical decomposition of excess azobis(4-cyano valeric acid) (ACVA) modified with an alkyne endgroup in the presence of the thiocarbonylthio-capped PS. The successful click endgroup modifications of several polystyrenes along with the results from the cyclization of a PS with Mn=4300gmol−1 are discussed in detail. This improved method avoids the presence of thiocarbonylthio functions in the macrocycle, thus considerably increasing the chemical stability of these polymers.
