SANS and SLS Studies on Tetra-Arm PEG Gels in As-Prepared and Swollen States

Matsunaga, Takuro; Sakai, Takamasa; Akagi, Yuki; Chung, Ung‐il; Shibayama, Mitsuhiro

doi:10.1021/ma901013q

Cited by 237 publications

(312 citation statements)

References 49 publications

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“…Figure 22 is a master plot of SANS curves for Tetra-PEG gels with various molecular weights, that is, -5K, -10K, -20K and -40K, prepared at various polymer concentrations, f 0 . 93 All of the SANS intensity functions could be superimposed with the reduced variables I(q)/ (f 0 x 2 ) and qx. For qx X10 À1 , the scattering functions fall onto a single master curve given by an Ornstein-Zernike function: 86,93 IðqÞ…”

Section: High-performance Polymer Gelsmentioning

confidence: 99%

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Small-angle neutron scattering on polymer gels: phase behavior, inhomogeneities and deformation mechanisms

Shibayama

2010

Polym J

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201

139

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Recent developments in small-angle neutron scattering (SANS) investigations on polymer gels are reviewed by encompassing (i) volume phase transition and microphase separation, (ii) inhomogeneities in polymer gels, (iii) pressure dependence of hydrophobic interaction and (iv) structural characterization of super-tough gels. These developments owe much to the understanding of gel inhomogeneities and advances in the precision analyses of SANS, such as the contrast variation method coupled with singular value decomposition and the accurate evaluation of incoherent scattering intensity. As one of the fruitful outcomes, deformation mechanisms in various types of super-tough gels are elucidated.

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Section: High-performance Polymer Gelsmentioning

confidence: 99%

“…93 All of the SANS intensity functions could be superimposed with the reduced variables I(q)/ (f 0 x 2 ) and qx. For qx X10 À1 , the scattering functions fall onto a single master curve given by an Ornstein-Zernike function: 86,93 IðqÞ…”

Section: High-performance Polymer Gelsmentioning

confidence: 99%

Small-angle neutron scattering on polymer gels: phase behavior, inhomogeneities and deformation mechanisms

Shibayama

2010

Polym J

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201

139

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“…To monitor gel dissolution, a trace amount of absorbing and/or fluorescent "erosion" probe was covalently attached by a stable linker to CO residues before hydrogel formation (19). Although we have not studied mechanical or structural properties of these gels, analogous Tetra-PEG gels have been intensively studied and shown to possess near-ideal homogeneous polymer network properties with minimal defects (8,9,20). In another format (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It was our desire to develop a system in which we could keep gel properties largely constant, and achieve different degradation rates by modifying the rate of gel scaffold cleavage. In the present work, we tether drugs or drug surrogates to large-pore hydrogels prepared from two multi-arm PEG macromonomers using β-eliminative linkers that cleave at desired rates of drug release; similar β-eliminative linkers having slower cleavage rates are used to cross-link four arms of each macromonomer to form Tetra-PEG gels (8,9). In this manner, either or both cleavage rates can be tuned to coordinate drug release and gel degradation without introducing major structural differences in the gels.…”

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confidence: 99%

Hydrogel drug delivery system with predictable and tunable drug release and degradation rates

Ashley

Henise

Reid

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

320

288

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Many drugs and drug candidates are suboptimal because of short duration of action. For example, peptides and proteins often have serum half-lives of only minutes to hours. One solution to this problem involves conjugation to circulating carriers, such as PEG, that retard kidney filtration and hence increase plasma half-life of the attached drug. We recently reported an approach to half-life extension that uses sets of self-cleaving linkers to attach drugs to macromolecular carriers. The linkers undergo β-eliminative cleavage to release the native drug with predictable half-lives ranging from a few hours to over 1 y; however, half-life extension becomes limited by the renal elimination rate of the circulating carrier. An approach to overcoming this constraint is to use noncirculating, biodegradable s.c. implants as drug carriers that are stable throughout the duration of drug release. Here, we use β-eliminative linkers to both tether drugs to and cross-link PEG hydrogels, and demonstrate tunable drug release and hydrogel erosion rates over a very wide range. By using one β-eliminative linker to tether a drug to the hydrogel, and another β-eliminative linker with a longer half-life to control polymer degradation, the system can be coordinated to release the drug before the gel undergoes complete erosion. The practical utility is illustrated by a PEG hydrogel-exenatide conjugate that should allow once-a-month administration, and results indicate that the technology may serve as a generic platform for tunable ultralong half-life extension of potent therapeutics.click chemistry | regenerative medicine | tetra-PEG C onjugation of drugs to macromolecular carriers is a proven strategy for improving pharmacokinetics. In one approach, the drug is covalently attached to a long-lived circulating macromolecule-such as PEG-through a linker that is slowly cleaved to release the native drug (1, 2). We have recently reported such conjugation linkers that self-cleave by a nonenzymatic β-elimination reaction in a highly predictable manner, and with half-lives of cleavage spanning from hours to over a year (3). In this approach, a macromolecular carrier is attached to a linker that is attached to a drug or prodrug via a carbamate group (1; Scheme 1); the β-carbon has an acidic carbon-hydrogen bond (C-H) and also contains an electron-withdrawing "modulator" (Mod) that controls the pK a of that C-H. Upon hydroxide ion-catalyzed proton removal to give 2, a rapid β-elimination occurs to cleave the linkercarbamate bond and release the free drug or prodrug and a substituted alkene 3. The rate of drug release is proportional to the acidity of the proton, and that is controlled by the chemical nature of the modulator; thus, the rate of drug release is controlled by the modulator. It was shown that both in vitro and in vivo cleavages were linearly correlated with electron-withdrawing effects of the modulators and, unlike ester bonds commonly used in releasable linkers (2), the β-elimination reaction was not catalyzed by general bases or ser...

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“…Tetra-PEG gels can be well fitted to available theoretical scattering functions (the Ornstein-Zernike function), and no observable excess scattering appears in the small-angle neutron scattering results. 46 Young's modulus of tetra-PEG gels is proportionally correlated to polymer volume fractions, indicating the absence of entanglements in the network. 47 It has been observed that the compressive strength of tetra-PEG gels is on the order of a few to tens of MPa for a 120 mg ml À1 gel made from a macromer with M w ¼10 000.…”

Section: Tetra-peg Gelsmentioning

confidence: 99%

Recent advances in hydrogels in terms of fast stimuli responsiveness and superior mechanical performance

Imran

Seki

Takeoka

2010

Polym J

139

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This review addresses the potential development of polymer hydrogels in terms of fast stimuli responsiveness and superior mechanical properties. The slow response and mechanical weakness of stimuli-sensitive hydrogels have been considered as the main barriers for their further development and practical application. It has been a dream of scientists to have fast stimuliresponsive hydrogels with superior mechanical performance. In this review, the principal reasons behind the poor stimulus sensitivity and mechanical strength of polymer gels are highlighted, and we present some pioneering physical and chemical efforts aimed at fabricating hydrogels with high stimuli sensitivities and/or superior mechanical properties. Polymer Journal ( Keywords: butterfly pattern; fast stimuli sensitivity; hydrogel; LCST; mechanical property INTRODUCTION Polymer hydrogels (hereafter called 'hydrogels') are three-dimensional polymer networks in which the voids are filled with water. These hydrogels are widely used in a variety of industrial and consumer products such as oil dewatering systems, mechanical absorbers, diapers and contact lenses. One of the most remarkable areas of research on hydrogels in the past few decades has been their stimulus sensitivity. Hydrogels composed of stimuli-responsive polymers reversibly alter their shape and volume in response to small variations in the environment, such as pH, temperature, light and electric and magnetic fields, thereby changing their physico-chemical characteristics. 1 Among all of the available environmentally responsive hydrogels, temperature-responsive hydrogels have attracted the most attention because of the facile tuning of their properties. In particular, poly(Nisopropylacrylamide) (poly(NIPA)) hydrogels have been widely investigated as thermosensitive hydrogels. Poly(NIPA) has a low critical solution temperature (LCST) at around 32 1C in water. The flexible coil of poly(NIPA) (soluble) converts into a compact globular state (insoluble) at the LCST, and this conformational change is reversible. 2 Thus, hydrogels composed of poly(NIPA) undergo a reversible volume change at a similar transition temperature in water. Poly(NIPA) hydrogels have potential applications in drug delivery systems, therapeutic agents, diagnostic devices, biomaterials, cell cultivation, biocatalysts, sensors, microfluidic devices, actuators, optical devices and size-selective separation among others. [3][4][5] A recent subject that has attracted much attention in the field of gel science is the fabrication of hydrogels with the rapid stimuli responsiveness and superior mechanical properties required for many applications of stimuli-responsive hydrogels. The creation of durable

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SANS and SLS Studies on Tetra-Arm PEG Gels in As-Prepared and Swollen States

Cited by 237 publications

References 49 publications

Small-angle neutron scattering on polymer gels: phase behavior, inhomogeneities and deformation mechanisms

Small-angle neutron scattering on polymer gels: phase behavior, inhomogeneities and deformation mechanisms

Hydrogel drug delivery system with predictable and tunable drug release and degradation rates

Recent advances in hydrogels in terms of fast stimuli responsiveness and superior mechanical performance

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