- Substituent Effects on the pH Sensitivity of Acetals and Ketals and Their Correlation with Encapsulation Stability in Polymeric Nanogels
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The effect of structural variations in acetal- and ketal-based linkers upon their degradation kinetics is studied through the design, synthesis, and study of six series of molecules, comprising a total of 18 different molecules. Through this systematic study, we show that the structural fine-tuning of the linkers allows access to variations in kinetics of degradation of more than 6 orders of magnitude. Hammett correlations show that the ρ value for the hydrolysis of benzylidene acetals is about ?4.06, which is comparable to an SN1-like process. This shows that there is a strong, developing positive charge at the benzylic position in the transition state during the degradation of acetals. This positively charged transition state is consistent with the relative degradation rates of acetals vs ketals (correlated to stabilities of 1°, 2°, and 3° carboxonium ion type intermediates) and the observed effect of proximal electron-withdrawing groups upon the degradation rates. Following this, we studied whether the degradation kinetics study correlates with pH-sensitive variations in the host-guest characteristics of polymeric nanogels that contains these acetal or ketal moieties as cross-linking functionalities. Indeed, the trends observed in the small molecule degradation have clear correlations with the encapsulation stability of guest molecules within these polymeric nanogels. The implications of this fundamental study extend to a broad range of applications, well beyond the polymeric nanogel examples studied here.
- Liu, Bin,Thayumanavan
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- Acid-degradable polymer-caged lipoplex (PCL) platform for siRNA delivery: Facile cellular triggered release of siRNA
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An acid-degradable polymer-caged lipoplex (PCL) platform consisting of a cationic lipoplex core and a biocompatible, pH-responsive polymer shell has been developed for the effective delivery of small interfering RNA (siRNA) through a combination of facile loading, rapid acid-triggered release, cellular internalization, and effective endosomal escape. In vitro testing of this degradable PCL delivery platform reveals ~45- and ~2.5-fold enhancement of enhanced green fluorescent protein knockdown in cancer cells in comparison to either free siRNA or siRNA-loaded non-acid-degradable lipoplex formulations, respectively.
- Hong, Bong Jin,Chipre, Anthony J.,Nguyen, Sonbinh T.
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- CROSSLINKED POLYMER NANO-ASSEMBLIES AND USES THEREOF
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The invention provides powerful methods and compositions for designing, selecting, fine-tuning and optimizing polymer nanogel and other supramolecular assemblies for various properties including, for example, particle size, density and morphology, guest l
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Paragraph 0226
(2019/04/08)
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- Crosslinked polymer nano-assemblies and uses thereof
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The invention provides powerful methods and compositions for designing, selecting, fine-tuning and optimizing polymer nanogel and other supramolecular assemblies for various properties including, for example, particle size, density and morphology, guest l
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Page/Page column 38; 39
(2017/11/14)
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- CROSSLINKED POLYMER NANO-ASSEMBLIES AND USES THEREOF
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The invention provides powerful methods and compositions for designing, selecting, fine-tuning and optimizing polymer nanogel and other supramolecular assemblies for various properties including, for example, particle size, density and morphology, guest l
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Paragraph 0227
(2015/08/04)
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- A novel strategy for encapsulation and release of proteins: Hydrogels and microgels with acid-labile acetal cross-linkers
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A new acid-labile acetal cross-linker was synthesized and used to prepare protein-loaded hydrogels and microgels. This cross-linker undergoes an acid-catalyzed degradation with a half-life of 5.5 min at pH 5.0 and 24 h at pH 7.4. Protein-loaded hydrogels were synthesized with this cross-linker, and their release profiles were measured as a function of pH. Hydrogels made with the acetal cross-linker release their contents in a pH-dependent manner. The acetal cross-linker was also used to synthesize microgels with sizes between 1 and 10 μm, a range suitable for phagocytosis. The unique acid sensitivity of the acetal cross-linker should make it a useful synthetic intermediate in the design of acid-sensitive drug or gene delivery systems. Copyright
- Murthy, Niren,Thng, Yi X.,Schuck, Stephany,Xu, Ming C.,Frechet, Jean M. J.
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p. 12398 - 12399
(2007/10/03)
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