Optically monitoring the microenvironment of a hydrophobic cargo in amphiphilic nanogels: influence of network composition on loading and release (original) (raw)
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2010
This paper describes the synthesis of styrene-based macromonomers with covalently attached model drugs (ibuprofen and naproxen) or fluorescent markers (pyrene) and their incorporation into linear or hyperbranched p-(chloromethyl)styrene copolymers. Alternatively the copolymers were produced by postpolymerization modification of linear or hyperbranched poly[p-(chloromethyl)styrene], PPCMSt, with the same compounds. The incorporation of these copolymers into amphiphilic conetworks was achieved by two methods: Williamson ether synthesis between PPCMSt and poly(ethylene glycol), PEG, with hydroxyl end groups or by nucleophilic substitution between the chloromethyl moieties in PPCMSt and the amine end groups in poly(oxyalkylenediamine), Jeffamine. The dynamic and equilibrium swelling properties were studied on representative Jeffamine hydrogels. The swelling studies showed that the conetworks absorb water quickly and reach equilibrium in 1-2 h, the equilibrium swelling ratio of gels based on linear or hyperbranched copolymer being 181-358% and 244-480%, respectively. Preliminary drug release studies in different aqueous media showed that the release kinetics and the amount of drugs released from hydrogels depend on the physical properties of drugs, the microstructure of polymer network, and the drug-polymer interaction and more particularly on the hydrolysis dynamics of ester linkage between the drug and the polymer matrix.
Journal of Polymer Science, 2021
Polymeric micro-and nanogels are defined by their water-swollen hydrophilic networks that can often impart outstanding biocompatibility and highcolloidal stability. Unfortunately, this highly hydrophilic nature limits their potential in areas where hydrophobic or amphiphilic interactions are required, for example, the delivery of hydrophobic cargoes or tailored interactions with amphipathic (bio-)surfaces. To overcome this limitation, amphiphilic microÀ/nanogels are emerging as new colloidal materials that combine properties from hydrogel networks with hydrophobic segments, known from solid hydrophobic polymer particles or micellar cores. The ability to accurately adjust the balance of hydrophobic and hydrophilic components in such amphiphilic colloidal systems enables new tailored properties. This opens up new applications ranging from the
Macromolecular Bioscience, 2006
Summary: Photocrosslinked nanogels with a hydrophobic core and hydrophilic shell are successfully fabricated with the goal of obtaining a biocompatible and biodegradable drug carrier for hydrophobic anticancer drugs. These nanogels are composed of amphiphilic triblock copolymers, poly(D,L‐lactic acid)/poly(ethylene glycol)/poly(D,L‐lactic acid) (PLA‐PEG‐PLA), with acrylated groups at the end of the PLA segments. The copolymers are synthesized by ring‐opening polymerization and possess a low CMC (49.6 mg · L−1), which easily helps to form micelles by self‐assembly. The acrylated end groups allow the micelles to be photocrosslinked by ultraviolet irradiation, which turn the micelles into nanogels. These nanogels exhibit excellent stability as a suspension in aqueous media at ambient temperature as compared to the micelles. Moreover, the size of the nanogels is easily manipulated in a range of 150 to 250 nm by changing the concentration of crosslinkers, e.g., ethylene glycol dimethacry...
Novel amphiphilic microgels fabricated via on-chip polymerisation
The 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2015), Gyeongju (Korea), 25 - 29 October, 2015
We report the on-chip polymerisation of hydrophobic microgels from precursor droplets, and their downstream synthesis to pH-responsive amphiphilic microgels for drug delivery. This elegant platform offers superior control over microgel properties, including size, crosslinking density and hydrophobic/hydrophilic properties. The encapsulation and release of hydrophilic (Trypan Blue) and hydrophobic (Sudan Red) dyes based on the microgel shrinking/swelling properties was also studied.
Controlled drug release from hydrogel nanoparticle networks
Journal of Controlled Release, 2004
Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-coacrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependant, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules. D
Bio-Orthogonal Nanogels for Multiresponsive Release
Biomacromolecules
Responsive nanogel systems are interesting for the drug delivery of bioactive molecules due to their high stability in aqueous media. The development of nanogels that are able to respond to biochemical cues and compatible with the encapsulation and the release of large and sensitive payloads remains challenging. Here, multistimuli-responsive nanogels were synthesized using a bio-orthogonal and reversible reaction and were designed for the selective release of encapsulated cargos in a spatiotemporally controlled manner. The nanogels were composed of a functionalized polysaccharide cross-linked with pH-responsive hydrazone linkages. The effect of the pH value of the environment on the nanogels was fully reversible, leading to a reversible control of the release of the payloads and a "stop-and-go" release profile. In addition to the pH-sensitive nature of the hydrazone network, the dextran backbone can be degraded through enzymatic cleavage. Furthermore, the cross-linkers were designed to be responsive to oxidoreductive cues. Disulfide groups, responsive to reducing environments, and thioketal groups, responsive to oxidative environments, were integrated into the nanogel network. The release of model payloads was investigated in response to changes in the pH value of the environment or to the presence of reducing or oxidizing agents.
AMPHIPHILIC MICROGELS FROM POLYMERISATION OF HYDROPHOBIC DROPLETS-NOVEL MICROGELS FABRICATED ON-CHIP
We report the synthesis of microgels for drug delivery via on-chip droplet generation and downstream photo-polymerization which affords control over hydrophobicity/hydrophilicity and enables the synthesis of amphiphilic microgels from hydrophobic droplets. The amphiphilic microgels were found to be effective for encapsulation and release of a hydrophobic dye (Sudan red) as an analog of a drug molecule.
Microfluidically fabricated pH-responsive anionic amphiphilic microgels for drug release
Journal of Materials Chemistry B, 2016
Amphiphilic microgels of different composition based on the hydrophilic, pH-responsive acrylic acid (AA) and the hydrophobic, non-ionic n-butyl acrylate (BuA) were synthesised using a lab-on-a-chip device. Hydrophobic droplets were generated via a microfluidic platform that contained a protected form of AA, BuA, the hydrophobic crosslinker, ethylene glycol dimethacrylate (EGDMA), and a free radical initiator in an organic solvent. These hydrophobic droplets were photopolymerised within the microfluidic channels and subsequently hydrolysed, enabling an integrated platform for the rapid, automated, and in situ production of anionic amphiphilic microgels. The amphiphilic microgels did not feature the conventional core–shell structure but were instead based on random amphiphilic copolymers of AA and BuA and hydrophobic crosslinks. Due to their amphiphilic nature they were able to encapsulate and deliver both hydrophobic and hydrophilic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the surrounding aqueous solution and the hydrophobic content of the microgels.
Journal of Polymer Science, Part A: Polymer Chemistry, 2018
Cationic, amphiphilic microgels of differing compositions based on hydrophilic, pH, and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and hydropho-bic, nonionic n-butyl acrylate (BuA) are synthesized using a lab-on-a-chip device. Hydrophobic oil-in-water (o/w) droplets are generated via a microfluidic platform, with the dispersed (droplet) phase containing the DMAEMA and BuA, alongside the hydrophobic cross-linker, ethylene glycol dimethacrylate, and a free radical initiator in an organic solvent. Finally, the hydrophobic droplets are photopolymerized via a UV light source as they traverse the microfluidic channel to produce the cationic amphiphilic microgels. This platform enables the rapid, automated, and in situ production of amphiphilic micro-gels, which do not match the core-shell structure of conventionally prepared microgels but are instead based on random amphiphilic copolymers of DMAEMA and BuA between the hydrophobic cross-links. The microgels are characterized in terms of their swelling and encapsulation abilities, which are found to be influenced by both the pH response and the hydro-phobic content of the microgels.