Multiple stimuli-responsive polymeric micelles for controlled release

Shah

et al. 2018

Macro Materials & Eng

A series of partially photodegradable o‐nitrobenzyl nanogels (NBNG) with different caged functional groups (COOH, OH, SH) are prepared and compared with a nondegradable nanogel as additives in photocurable materials. Photoinduced nanogel network disruption and photoinitiated polymerization of infiltrating and dispersing monomer could be controlled independently. In triethylene glycol dimethacrylate (TEGDMA), o‐NBNGs that release a COOH or OH functional group upon photodegradation of the o‐nitrobenzyl crosslinker, the reduced chemical crosslinking density of the nanogel network allows greater penetration of monomer into the partially degraded nanogel network, which results in an increase in volumetric shrinkage and polymerization stress. In contrast, the formulation of o‐NBNGs with caged SH groups also can be photodegraded but is able to rebuild the chemical crosslinking through thiol‐based chain transfer reactions when photocured as a dispersion in TEGDMA. As such, it behaves like a photo‐inert nanogel. Dynamic thermomechanical analysis and testing by three‐point bending further confirms the photoinduced crosslink density variation influences mechanical properties of the final polymer networks. This work demonstrates the inherent properties of the nanogel network and the type of crosslinking can alter the performance of the photocured resin while a separate photochemical process can be used to regulate photoinduced polymerization.

Section: Introductionmentioning

confidence: 99%

Effects of Photodegradable o‐Nitrobenzyl Nanogels on the Photopolymerization Process

Shah

et al. 2018

Macro Materials & Eng

Macromolecular Bioscience

“…Meanwhile, the low critical micelle concentration (CMC) of amphiphilic block copolymers benefits the micelles with high antidilution ability and stability in blood circulatory system . In recent years, researchers have made numerous efforts on stimuli‐responsive micelles for achieving more efficient targeted and controlled release of drugs . Such drug release behaviors can be realized by using stimuli‐responsive micelles constructed from responsive block polymers; they can respond to environmental stimuli and then release encapsulated drugs controllably.…”

Section: Introductionmentioning

confidence: 99%

K⁺‐Responsive Block Copolymer Micelles for Targeted Intracellular Drug Delivery

Yan

Wan

et al. 2017

In this work, a novel type of block copolymer micelles with K -responsive characteristics for targeted intracellular drug delivery is developed. The proposed smart micelles are prepared by self-assembly of poly(ethylene glycol)-b-poly(N-isopropylacry-lamide-co-benzo-18-crown-6-acrylamide) (PEG-b-P(NIPAM-co-B18C6Am)) block copolymers. Prednisolone acetate (PA) is successfully loaded into the micelles as the model drug, with loading content of 4.7 wt%. The PA-loaded micelles display a significantly boosted drug release in simulated intracellular fluid with a high K concentration of 150 × 10 m, as compared with that in simulated extracellular fluid. Moreover, the in vitro cell experiments indicate that the fluorescent molecules encapsulated in the micelles can be delivered and specifically released inside the HSC-T6 and HepG2 cells responding to the increase of K concentration in intracellular compartments, which confirms the successful endocytosis and efficient K -induced intracellular release. Such K -responsive block copolymer micelles are highly potential as new-generation of smart nanocarriers for targeted intracellular delivery of drugs.

“…Linear-dendritic copolymers that can respond to the external stimuli such as pH, temperature, redox, light, and enzyme have been investigated for their self-assembly and stimuli-responsive disassembly in aqueous solution. [23][24][25][26] Among the stimuli-responsive nanocarriers, pH-degradable micelles have attracted lot of interest because of existence of a pH gradient between the intra and extracellular environment of cancer cells. Such linkages can be incorporated in the side chain or at the junction of the two blocks.…”

Section: Introductionmentioning

confidence: 99%

Controlled micellar disassembly of photo- and pH-cleavable linear-dendritic block copolymers

2015

A linear-dendritic block copolymer with both photo-and pH-cleavable linkages at the junction between the hydrophobic dendron and hydrophilic linear polymer was synthesised. The photocleavable o-nitrobenzyl group attached to alkyne was introduced at the focal point of polyester dendron and acid-degradable acetal linkage with terminal azide was introduced at one end of linear polyethylene glycol. The two segments were connected using click chemistry. The copolymer was found to self-assemble into micelle-like aggregates in dilute aqueous solution. Stimuli-responsive disassembly of the aggregates was studied by monitoring fluorescence emission of the encapsulated hydrophobic dye and dynamic light scattering (DLS). Products of acetal cleavage at acidic pH were analyzed by gel permeation chromatography and NMR spectroscopy. The photo and pH stimuli were applied separately as well as simultaneously to study the rate of dye release.Synergistic effect of the two stimuli on dye release was demonstrated and non-cytotoxic nature of the polymer was shown using MTT assay. Cell uptake of DOX-loaded micelles and photo-induced release of the drug resulting in significantly higher cytotoxicity than by free DOX was demonstrated using MDA-MB-231 cells.6 was replaced by fresh growth media and the cells were allowed to grow for further 24h under the same culture condition. Cellular uptake and intra-cellular DOX release studied by epifluorescence microscopyMDA-MB-231 cells were seeded in 24 well plate at a density of 50,000 cells/well in DMEM containing 10% FBS. The plate was incubated at 37 °C with 5% CO 2 for 24h. After incubation the media was replaced with DOX-loaded micelles, incubated for 2 h and irradiated under UV light (365nm) for 30 minutes. At the end, cells were washed 3 times with PBS and fixed with 4% paraformaldehyde. Nucleus was stained with DAPI. Images were acquired using epifluorescence microscope by Carl Zeiss (Model: Axio Observer.Z1, Oil emersion objective, 63X). (Filters set 49 DAPI shift free EX G 365, BS FT 395, EM BP 445/50, Filter set 20 Rhodamin shift freeEX BP 54.6112, BS FT 560, EM BP 575-640). Results and discussionSynthesis. Bis-MPA-based polyester dendron and polyethylene glycol (PEG) were selected as hydrophobic and hydrophilic components of the block copolymer, respectively. The o-nitrobenzyl (ONB) group is known to cleave under UV irradiation as well as by two photon absorption in the near infrared (NIR) region 34,43 while acetal linkage is known to cleave under mild acidic conditions. 28,44 Moreover, there is large difference in their rates of cleavage so that drug release can be fine tuned by controlling the time of exposure.