Novel Nanogels with Both Thermoresponsive and Hydrolytically Degradable Properties

Huang, Xiao; Misra, Gauri P.; Vaish, Amit; Flanagan, John M.; Sutermaster, Bryan A.; Lowe, Timothy J.

doi:10.1021/ma800081g

Cited by 32 publications

(19 citation statements)

References 25 publications

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“…Line profiles taken from these images permit estimation of the dried microgel heights and diameters. The height/diameter ratio provides a rough, qualitative estimate of microgels stiffness [29]; this analysis suggests that the APS-initiated microgels (μG5 and μG6) are somewhat stiffer than those prepared with V50 (Figure 1f), presumably due to increased cross-linking brought about by the aforementioned chain transfer reactions.…”

Section: Resultsmentioning

confidence: 99%

Physical Aging and Phase Behavior of Multiresponsive Microgel Colloidal Dispersions

et al. 2009

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Quantitative microscopy measurements have been made on poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-AAc) microgel dispersions as a function of time, temperature, pH, and volume fraction. These studies reveal an extreme degree of complexity in the physical aging and phase behavior of the dispersions; this complexity arises from a convolution of the system energetics at the colloidal, polymer-chain, and molecular scales. Superficially, these dispersions display the classic colloidal phases observed for spherical particles (i.e., gas, fluid, crystal, and glass). However, unlike simple repulsive hard spheres, pNIPAm-AAc dispersions are observed to evolve from a diffusive, fluidlike state immediately after being introduced into rectangular capillary tubes, to very slow crystalline or glassy phases after days or weeks of aging. In addition to this structural evolution, the free volume accessible to the microgels in crystalline or glassy phases (i.e., the cage size) decreases with time, indicating that the physical aging process does not end following assembly, but instead continues to evolve as the dispersion slowly proceeds to an equilibrium state. The temperature dependence of pNIPAm-AAc microgel swelling and how it influences the colloidal assembly was evaluated during the aging process as well. These thermal melting experiments revealed an enhancement in the thermal stability (i.e., a decrease in the influence of temperature on the phase behavior) of the assemblies during the aging process that we associate with an evolution of attractive interparticle interactions during aging. These attractive interactions dictate the time scale for assembly (aging), the final phase adopted by the dispersion, the dynamics of the final state, and the ultimate thermal stability. The culmination of these studies is the pseudoequilibrium phase behavior of pNIPAm-AAc microgel dispersions, which we present as a function of pH and volume fraction following approximately 1 month of aging. This diagram reveals highly complex dispersion characteristics that appear to be intrinsically tied to the degree of AAc protonation. In general, we find that, at pH < pK(a), the final dispersions behave in a manner that can be associated with attractive interparticle interactions, whereas at pH > pK(a), repulsive interactions appear to be dominant. These results are discussed in the context of the slow evolution of microgel swelling and attractive interaction potentials arising from reorganization and association of polymer chains via multiple weak hydrogen-bonding interactions.

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Section: Resultsmentioning

confidence: 99%

Physical Aging and Phase Behavior of Multiresponsive Microgel Colloidal Dispersions

et al. 2009

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“…Crosslinkers that degrade or hydrolyze in response to different endogenous stimuli such as acidic pH (e.g. 2,2-dimethacroyloxy-1-ethoxypropane [24,74], HEMA-lactate-Dextran [75–78], poly(l-lactic acid)[79]), redox potential (e.g. bis(2-methacryloyloxyethyl) disulfide [80] and disulfide-containing crosslinker N,N’- bis(acryloyl) cystamine [40]) or enzymes (e.g.…”

Section: Thermoresponsive Nanomaterialsmentioning

confidence: 99%

Design strategies for physical-stimuli-responsive programmable nanotherapeutics

Sahle

Gulfam

Lowe

2018

Drug Discovery Today

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Nanomaterials that respond to externally applied physical stimuli such as temperature, light, ultrasound, magnetic field and electric field have shown great potential for controlled and targeted delivery of therapeutic agents. However, the body of literature on programming these stimuli-responsive nanomaterials to attain the desired level of pharmacologic responses is still fragmented and has not been systematically reviewed. The purpose of this review is to summarize and synthesize the literature on various design strategies for simple and sophisticated programmable physical stimuli-responsive nanotherapeutics.

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“…1) with DP ¼ 8 (the lactide chain length of the lactate unit) and DS ¼ 15 (the average number of cross-linkable chains per dextran) were synthesized using the procedure described previously 32,33 with the feeding ratios of precursors modified accordingly. The DP and DS of the macromers were estimated from the 1 H NMR spectra.…”

Section: Synthesis Of Hydrogelsmentioning

confidence: 99%

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

Imai

Misra

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration.METHODS. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. RESULTS.The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH ¼ 7.4) at 378C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week.CONCLUSIONS. The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.

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Novel Nanogels with Both Thermoresponsive and Hydrolytically Degradable Properties

Cited by 32 publications

References 25 publications

Physical Aging and Phase Behavior of Multiresponsive Microgel Colloidal Dispersions

Physical Aging and Phase Behavior of Multiresponsive Microgel Colloidal Dispersions

Design strategies for physical-stimuli-responsive programmable nanotherapeutics

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

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