Polyplex Formation Influences Release Mechanism of Mono- and Di-Valent Ions from Phosphorylcholine Group Bearing Hydrogels

Wilson, A. Nolan; Blenner, Mark; Guiseppi‐Elie, Anthony

doi:10.3390/polym6092451

Cited by 17 publications

(13 citation statements)

References 53 publications

(63 reference statements)

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“…∞ is the fractional drug release at time t, τ is the lag time, b is the fractional drug burst release, k is a kinetic constant that measures the drug release rate characteristic of the drug/polymer system, and n is the release exponent which characterizes the drug release mechanism [52][53][54][55][56][57][58] .…”

Section: Photochemical Degradation Of Melatoninmentioning

confidence: 99%

PolyRad – Protection Against Free Radical Damage

Kim

Tse

Webb

et al. 2020

Sci Rep

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The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H 2 o 2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H 2 o 2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H 2 o 2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dosedependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration ~ 0.01 mg ml / (g ml 10 /). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications. As NASA prepares for exploration missions beyond low Earth orbit with no opportunities for resupply, pharmaceutical instability may present significant risk to the crew health due to the loss of efficacy over time. Astronauts suffer from sleep disruption during space flight that can affect their mental and physical health in performing routine work 1-4. Therefore, mitigation against the effects of space radiation on pharmaceutical drugs is necessary for the success of long-term space missions. NASA is primarily concerned with the he...

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Section: Photochemical Degradation Of Melatoninmentioning

confidence: 99%

PolyRad – Protection Against Free Radical Damage

Kim

Tse

Webb

et al. 2020

Sci Rep

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“…The release data were approximated with application of Higuchi (Equation (4)) and Korsmeyer–Peppas (Equation (5)) release models [30,31]: Q = K H t 1/2 . Log(M t /M ∞ ) = Logk + nLogt.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Delivery of 4-Thioureidoiminomethylpyridinium Perchlorate in Tuberculosis Models with IgG Functionalized Poly(Lactic Acid)-Based Particles

et al. 2018

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The compound 4-thioureidoiminomethylpyridinium perchlorate (perchlozone©) is a novel anti-tuberculosis drug that is active in multiple drug resistance cases, but the compound is hepatotoxic. To decrease the systemic load and to achieve targeting, we encapsulated the drug into poly(lactic acid)-based micro- (1100 nm) and nanoparticles (170 nm) that were modified with single-chain camel immunoglobulin G (IgG) for targeting. Both micro- and nanoparticles formed stable suspensions in saline solution at particle concentrations of 10–50 mg/mL. The formulations were injected intraperitoneally and intravenously into the mice with experimental tuberculosis. The survival of control animals was compared to that of mice which were treated with daily oral drug solution, single intraperitoneal administration of drug-loaded particles, and those treated both intravenously and intraperitoneally by drug-loaded particles modified with polyclonal camel IgGs. The distribution of particles in the organs of mice was analyzed with immunofluorescence and liquid chromatography/mass spectrometry. Morphological changes related to tuberculosis and drug toxicity were registered. Phagocytic macrophages internalized particles and transported them to the foci of tuberculosis in inner organs. Nanoparticle-based drug formulations, especially those with IgG, resulted in better survival and lower degree of lung manifestations than the other modes of treatment.

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“…Clearly, to a first approximation and in the absence of virtual crosslinks and polyplex formation [25], highly cross-linked polymer networks will exhibit lower swelling than loosely cross-linked networks and thus have smaller swelling factors, smaller molecular weights between crosslinks, lower degrees of hydration, and lower porosity or void fraction. With respect to their pore size and pore size distribution, hydrogels may be divided into macroporous, microporous or nonporous architectures.…”

Section: Degree Of Hydration ðWt%þ ¼mentioning

confidence: 99%

“…tetra(ethylene glycol) diacrylate (TEGDA), which, when added at varying concentrations, influence the modulus and the void volume through the cross-link density of the hydrogel [14,21]. However, such crosslinks may in addition be virtual and thus arise from hydrogen bonding [22,23], electrostatic interactions [24], polyplex formation [25], and molecular physical entanglements. Moreover, these hydrogels may be readily molecularly engineered to contain a wide variety of pendant and crosslinking bioactive moieties that render them biologically responsive wherein the response of the hydrogel is triggered by recognition of a biological agent conferred by an immobilized biorecognition species.…”

Section: Introductionmentioning

confidence: 99%

Partitioning of coomassie brilliant blue into DMAEMA containing poly(HEMA)-based hydrogels

Kotanen

Janagam

Idziak

et al. 2015

European Polymer Journal

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a b s t r a c tThe loading and release of anti-inflammatory drugs from hydrogel-coated implantable devices is a demonstrated approach in mitigating the inflammatory response of implantable devices. Poly(2-hydroxyethyl methacrylate)-based hydrogels possessing ionizable 2-(dimethylamino)ethyl methacrylate (DMAEMA) and cross-linked with varying concentrations (1, 3, 5, 7, 9 and 12 mol%) tetra(ethylene glycol) diacrylate (TEGDA) were synthesized and studied for their degree of hydration, glass transition temperature and partitioning of zwitterionic Coomassie Brilliant Blue (CBB), a zwitterionic drug surrogate known to bind to amines. Using UV-Vis spectroscopy, the partition coefficient of CBB within the hydrogels was found to average 6.69 ± 0.12 but to rise monotonically from 6.54 (1 mol%) to 6.84 (12 mol%) as a function of TEGDA mol% or cross-link density in accord with a monotonic reduction of the degree of hydration. The absence of DMAEMA was found to reduce the partition coefficient of CBB from 6.5 to 4.1. Both formulations, with and without DMAEMA (pK a = 7.5), showed an independence of pH over the physiologically relevant range, pH 5-pH 9, confirming that this difference was not due to Henderson-Hasselbalch ionization of the pendant group. The presence of DMAEMA resulted in a 1.44 fold increase in CBB loading confirming complex formation. The absence of DMAEMA still resulted in considerable partitioning of CBB into the hydrogel suggesting that the affinity between CBB and DMAEMA may not be the only relationship controlling the partition coefficient.

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Polyplex Formation Influences Release Mechanism of Mono- and Di-Valent Ions from Phosphorylcholine Group Bearing Hydrogels

Cited by 17 publications

References 53 publications

PolyRad – Protection Against Free Radical Damage

PolyRad – Protection Against Free Radical Damage

Enhanced Delivery of 4-Thioureidoiminomethylpyridinium Perchlorate in Tuberculosis Models with IgG Functionalized Poly(Lactic Acid)-Based Particles

Partitioning of coomassie brilliant blue into DMAEMA containing poly(HEMA)-based hydrogels

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