Dually Responsive Microgels from Polyether-Modified Poly(acrylic acid):  Swelling and Drug Loading

Bromberg, Lev; Temchenko, Marina; Hatton, T. Alan

doi:10.1021/la011868l

Cited by 134 publications

(150 citation statements)

References 43 publications

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“…Moreover, incorporation of different Poloxamer copolymers into microgels strongly influenced structure, swelling, and aggregation behavior of these gel microparticles [127]. As already mentioned these copolymers are characterized by a certain degree of mucoadhesiveness.…”

Section: Pharmaceutical Applicationsmentioning

confidence: 88%

“…At a polymer concentration of 5% release kinetics of LHRH followed a zero-order rate. Poloxamer-PAA copolymers can be additionally cross-linked by divinyl cross-linkers, resulting in permanent microgel particles [127].…”

Section: Pharmaceutical Applicationsmentioning

confidence: 99%

“…ratios) of basic molecules such as doxorubicin and can be loaded with anticancer agents [127,128]. Moreover, incorporation of different Poloxamer copolymers into microgels strongly influenced structure, swelling, and aggregation behavior of these gel microparticles [127].…”

Section: Pharmaceutical Applicationsmentioning

confidence: 99%

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Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

et al. 2011

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Self-assembling block copolymers (poloxamers, PEG/PLA and PEG/PLGA diblock and triblock copolymers, PEG/polycaprolactone, polyether modified poly(Acrylic Acid)) with large solubility difference between hydrophilic and hydrophobic moieties have the property of forming temperature dependent micellar aggregates and, after a further temperature increase, of gellifying due to micelle aggregation or packing. This property enables drugs to be mixed in the sol state at room temperature then the solution can be injected into a target tissue, forming a gel depot in-situ at body temperature with the goal of providing drug release control. The presence of micellar structures that give rise to thermoreversible gels, characterized by low toxicity and mucomimetic properties, makes this delivery system capable of solubilizing water-insoluble or poorly soluble drugs and of protecting labile molecules such as proteins and peptide drugs.

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Section: Pharmaceutical Applicationsmentioning

confidence: 88%

Section: Pharmaceutical Applicationsmentioning

confidence: 99%

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Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

et al. 2011

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“…9 The controlled use of microgels as delivery systems for peptide and protein drugs requires a basic understanding of the factors determining peptide/protein loading into, distribution within, and release from, microgels, and how these effects can be controlled by various design elements and external conditions. For microgel dispersions, there have been an increasing number of mechanistic studies dedicated to the effect of microgel properties, e.g., charge 10 and cross-linking density 11 , as well as of peptide properties, such as molecular weight 12 , charge (distribution) 10 , secondary structure 13 , and hydrophobicity 14 , including also effects of biodegradation of both the peptide 15 and microgel network 16 . For surface-bound microgels, on the other hand, there is very limited prior work done in this context.…”

Section: Introductionmentioning

confidence: 99%

Factors Affecting Peptide Interactions with Surface-Bound Microgels

et al. 2016

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Effects of electrostatics and peptide size on peptide interactions with surfacebound microgels were investigated with ellipsometry, confocal microscopy, and atomic force microscopy (AFM). Results show that binding of cationic poly-L-lysine (pLys) to anionic, covalently immobilized, poly(ethyl acrylate-co-methacrylic acid) microgels increased with increasing peptide net charge and microgel charge density. Furthermore, peptide release was facilitated by decreasing either microgel or peptide charge density. Analogously, increasing ionic strength facilitated peptide release for short peptides. As a result of peptide binding, the surface-bound microgels displayed pronounced deswelling and increased mechanical rigidity, the latter quantified by quantitative nanomechanical mapping. While short pLys was found to penetrate the entire microgel network and to result in almost complete charge neutralization, larger peptides were partially excluded from the microgel network, forming an outer peptide layer on the microgels. As a result of this difference, microgel flattening was more influenced by the lower Mw peptide than the higher. Peptide-induced deswelling was found to be lower for higher Mw pLys, the latter effect not observed for the corresponding microgels in the dispersed state. While the effects of electrostatics on peptide loading and release were similar to those observed for dispersed microgels, there were thus considerable effects of the underlying surface on peptide-induced microgel deswelling, which need to be considered in the design of surface-bound microgels as carriers of peptide loads, e.g., in drug delivery or in functionalized biomaterials.

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“…This can be achieved by several approaches including, among others, the embedding of hydrophobic drugs into either non-swollen hydrophobic polymeric nanoparticles and their stimuli-induced swelling 109,304 or into hydrophobic domains in hydrophilic microgels. 308 The covalent attachment of a drug to a hydrophilic polymeric carrier system via a cleavable molecule and the triggered degradation of the linker is another promising method. [301][302] Investigations on light-sensitive materials based on both of the described concepts are part of this thesis and were described in previous chapters (see chapter 5.3 and 5.4).…”

Section: Towards Stimuli-responsive Core/shell Nanoparticles Containimentioning

confidence: 99%

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Klinger

2013

Springer Theses

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This thesis focuses on the design, synthesis and characterization of novel photo-sensitive microgels and nanoparticles as potential materials for the loading and light-triggered release/accessibility of functional compounds. In order to realize this concept, different approaches to irradiation-dependent response mechanisms have been investigated.Novel light-cleavable divinyl functionalized monomeric crosslinkers based on o-nitrobenzyl derivatives were synthesized and used for the preparation of either PMMA or hydroxyl functionalized PHEMA microgels swellable and degradable in organic solvents. By the introduction of anionic MAA moieties into the PHEMA microgels, this concept was successfully transferred to double stimuli-responsive p(HEMA-co-MAA) hydrogel nanoparticles exhibiting a pH-dependent swelling and light-induced degradation behavior in aqueous media. This sensitivity to two orthogonal triggers is proposed to combine a pHinduced post-formation loading mechanism with a pH-and light-triggered release. In addition, a new class of enzyme-and light-sensitive PAAm microgels based on (meth-)acrylate functionalized dextrans as photo-and enzymatically degradable macromolecular crosslinkers was developed by introducing a photo-labile linker between the enzymatically degradable dextran chain and the polymerizable vinyl moieties. Here, the water solubility of the crosslinkers is assumed to enable an in situ loading approach of hydrophilic compounds.A different approach to the loading of microgels is based on photo-labile covalent microgel-drug conjugates. The first step to the realization of this concept was achieved by the development of a novel functional monomer consisting of a doxorubicin molecule covalently attached to a radically polymerizable methacrylate group via a photo-cleavable linker.Moreover, in order to enable the release of hydrophobic substances in aqueous media, hydrophobic nanoparticles consisting of a photo-resist polymer were designed to be degradable upon irradiation in water. Light-triggered conversion of the initial hydrophobic polymer into hydrophilic PMAA induced in situ particle dissolution and release of nile red.Since the introduction of a stimuli-responsive shell around a microgel is assumed to prevent leakage of embedded compounds, studies on non-stimuli-responsive shell formation around preformed microgel seed particles and the formation of microgel cores in polymeric shells were conducted to investigate potential synthetic pathways to this approach.In a last attempt, the surface of PHEMA and p(HEMA-co-MAA) microgels was functionalized with cinnamoyl groups in order to trigger the (reversible) particles interaction with each other by light-induced [2+2] cycloaddition reactions.

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Dually Responsive Microgels from Polyether-Modified Poly(acrylic acid): Swelling and Drug Loading

Cited by 134 publications

References 43 publications

Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

Factors Affecting Peptide Interactions with Surface-Bound Microgels

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

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