In vitro biocompatibility of magnetic thermo-responsive nanohydrogel particles of poly(N-isopropylacrylamide-co-acrylic acid) with Fe3O4 cores: Effect of particle size and chemical composition

Chou, Feng-Yi; Lai, Jui‐Yang; Shih, Chao‐Ming; Tsai, Meng-Chao; Lue, Shingjiang Jessie

doi:10.1016/j.colsurfb.2012.11.030

Cited by 33 publications

(13 citation statements)

References 53 publications

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“…The LCST represents the temperature at which a polymer chain shows a coil-to-globule transition in aqueous solution. 33 We have demonstrated that both the polymer concentration 4 and molecular weight of grafted PNIPAAm chains 5 may cause drastic effects on LCST of GN materials. When dissolved in deionized water, these biodegradable in situ gelling copolymers have a LCST of around 32°C.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems

Lai

Luo²

2015

Biomacromolecules

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In clinical ophthalmology, oxidative stress has been proposed as the initiating cause of ocular hypertension, which is one of the risk factors for glaucomatous damage and disease progression. In an attempt to improve the therapeutic efficacy of intracamerally administered pilocarpine, herein, a cytoprotective antiglaucoma drug delivery system composed of antioxidant gallic acid (GA)-functionalized gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling copolymer was developed for the first time. Analyses by UV-vis and Fourier transform infrared spectroscopies showed the formation of biopolymer-antioxidant covalent linkages in GNGA structures through a radical reaction in the presence of water-soluble redox initiators. The synthesized GNGA polymers with strong free radical scavenging effectiveness exhibited appropriate phase transition temperature and degradation rate as injectable bioerodible depots for minimally invasive pilocarpine delivery to the ocular anterior chamber. During the 2-week in vitro study, the sustained releases of sufficient amounts of pilocarpine for a therapeutic action in alleviating ocular hypertension could be achieved under physiological conditions. Results of cell viability, intracellular reactive oxygen species level, and intracellular calcium concentration indicated that the incorporation of antioxidant GA into GN structure can enhance cytoprotective effects of carrier materials against hydrogen peroxide-induced oxidative stress in lens epithelial cultures. Effective pharmacological responses (i.e., reduction of intraocular pressure and preservation of corneal endothelial cell morphology and density) in rabbits receiving intracameral GNGA injections containing pilocarpine were evidenced by clinical observations. The findings of in vivo studies also support the hypothesis that the GNGA carriers are more advantageous over their GN counterparts for the improvement of total antioxidant status in glaucomatous eyes with chronic ocular hypertension. The synthesized multifunctional molecules may be further used as potential polymer therapeutics for intraocular delivery of bioactive agents.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems

Lai

Luo²

2015

Biomacromolecules

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“…Human corneal endothelial cells can adhere and proliferate on the hydrophobic PNIPAAm-grafted surfaces at body temperature, and spontaneously detach from the hydrophilic substrates when the surrounding temperature is reduced to a level below the LCST. Furthermore, we recently examined the role of particle size and chemical composition in the determination of in vitro biocompatibility of magnetic thermoresponsive nanohydrogel particles of poly(NIPAAm-co-acrylic acid) with Fe 3 O 4 cores 15. These nanohydrogel carriers may exhibit controlled drug release to a target tissue under magnetic fields.…”

Section: Introductionmentioning

confidence: 99%

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio

Lai¹

2013

DDDT

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Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations.

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“…Biocompatibility refers to the ability of a biomaterial to perform with an appropriate host response in a specific situation 27 28 29 30 . It is an important property that blood-contacting biomaterials should possess for clinical use 31 32 33 .…”

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confidence: 99%

Low toxicity and long circulation time of Polyampholyte-coated magnetic nanoparticles for blood pool contrast agents

Wang

Shen

Zhao

et al. 2015

Sci Rep

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Polyampholyte-coated (poly(acrylic acid) (PAA)-co-3-(diethylamino)-propylamine (DEAPA)) magnetite nanoparticles (PAMNPs) have been prepared as contrasting agent used in magnetic resonance imaging (MRI). Excellent biocompatibility is required for contrasting agents used in high-resolution magnetic resonance angiography. To evaluate the biocompatibility of PAMNPs, some experiments have been conducted. The hemolysis, plasma recalcification, dynamic blood clotting, prothrombin time, inflammatory cytokine release and complement system activation assays were carried out to investigate the hemocompatibility. To evaluate the toxicity to vessel, MTT test and vascular irritation tests were conducted. Tissue toxicity test was also performed to investigate the biocompability in vivo. We also looked into the biodistribution. The results showed that PAMNPs at the working concentration (0.138 mM) present similar hemocompatibility with negative control, thus have no significant effect to vessels. PAMNPs were mainly distributed in the liver and the blood. The circulation time in blood was considerably long, with the half-time of 3.77 h in plasma. This property is advantageous for PAMNPs' use in angiography. PAMNPs could be metabolized rapidly in mice and were not observed to cause any toxic or adverse effect. In short, these results suggest that the PAMNPs have great potential to serve as safe contrast agents in magnetic resonance imaging (MRI).

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In vitro biocompatibility of magnetic thermo-responsive nanohydrogel particles of poly(N-isopropylacrylamide-co-acrylic acid) with Fe3O4 cores: Effect of particle size and chemical composition

Cited by 33 publications

References 53 publications

Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems

Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio

Low toxicity and long circulation time of Polyampholyte-coated magnetic nanoparticles for blood pool contrast agents

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