Effects of Peptide Secondary Structure on the Interaction with Oppositely Charged Microgels

Månsson, Ronja; Bysell, Helena; Hansson, Per; Schmidtchen, Artur; Malmsten, Martin

doi:10.1021/bm101165e

Cited by 28 publications

(21 citation statements)

References 47 publications

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“…In many applications the polyelectrolyte networks are spherical microgel particles with diameters in the range 10–1000 µm. There are a number of research papers showing that proteins and peptides can be loaded onto such microgels at low ionic strength and subsequently released at elevated ionic strengths [ 4 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The electrostatic interaction with the charged network does not seem to denature the molecules; instead the environment inside the microgel has been shown to protect them against degrading species [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Drug-Induced Phase Separation in Polyelectrolyte Microgels

Al-Tikriti

Hansson

2021

Gels

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Polyelectrolyte microgels may undergo volume phase transition upon loading and the release of amphiphilic molecules, a process important in drug delivery. The new phase is “born” in the outermost gel layers, whereby it grows inward as a shell with a sharp boundary to the “mother” phase (core). The swelling and collapse transitions have previously been studied with microgels in large solution volumes, where they go to completion. Our hypothesis is that the boundary between core and shell is stabilized by thermodynamic factors, and thus that collapsed and swollen phases should be able to also coexist at equilibrium. We investigated the interaction between sodium polyacrylate (PA) microgel networks (diameter: 400–850 µm) and the amphiphilic drug amitriptyline hydrochloride (AMT) in the presence of NaCl/phosphate buffer of ionic strength (I) 10 and 155 mM. We used a specially constructed microscopy cell and micromanipulators to study the size and internal morphology of single microgels equilibrated in small liquid volumes of AMT solution. To probe the distribution of AMT micelles we used the fluorescent probe rhodamine B. The amount of AMT in the microgel was determined by a spectrophotometric technique. In separate experiments we studied the binding of AMT and the distribution between different microgels in a suspension. We found that collapsed, AMT-rich, and swollen AMT-lean phases coexisted in equilibrium or as long-lived metastable states at intermediate drug loading levels. In single microgels at I = 10 mM, the collapsed phase formed after loading deviated from the core-shell configuration by forming either discrete domains near the gel boundary or a calotte shaped domain. At I = 155 mM, single microgels, initially fully collapsed, displayed a swollen shell and a collapsed core after partial release of the AMT load. Suspensions displayed a bimodal distribution of swollen and collapsed microgels. The results support the hypothesis that the boundary between collapsed and swollen phases in the same microgel is stabilized by thermodynamic factors.

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Section: Introductionmentioning

confidence: 99%

Drug-Induced Phase Separation in Polyelectrolyte Microgels

Al-Tikriti

Hansson

2021

Gels

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“…Most of the work done regarding microgels with antimicrobial activity deals with the drug delivery ability of microgels capable to carry and release antibiotics or antimicrobial agents [22,23,24,25]. Malmsten et al first studied the existing interactions between antimicrobial peptides (AMP) and poly(acrylic acid) microgels and peptide uptake and sustained release [26,27,28]. In a more recent study, they also studied key factors for the encapsulation and further release of AMP from poly(ethyl acrylate- co -methacrylic acid) anionic microgels by analyzing the effect of microgels different charge density in the AMP uptake/release [29].…”

Section: Introductionmentioning

confidence: 99%

Thermoresponsive Poly(N-Isopropylacrylamide-co-Dimethylaminoethyl Methacrylate) Microgel Aqueous Dispersions with Potential Antimicrobial Properties

et al. 2019

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The work herein describes the preparation of thermoresponsive microgels with potential antimicrobial properties. Most of the work performed so far regarding microgels with antimicrobial activity, deals with the ability of microgels to carry and release antibiotics or antimicrobial agents (antimicrobial peptides). The originality of this work lies in the possibility of developing intrinsic antimicrobial microgels by copolymerization of the well-known thermoresponsive monomer, N-isopropylacrylamide (NIPAM) with dimethylaminoethyl methacrylate (DMAEMA), a water-soluble monomer, to form microgels via precipitation polymerization (radical polymerization). Due to the presence of a tertiary amine in the DMAEMA comonomer, microgels can be modified by N-alkylation reaction with methyl and butyl iodide. This quaternization confers positive charges to the microgel surfaces and thus the potential antimicrobial activity. The effect of DMAEMA content and its quaternization with both, methyl and butyl iodide is evaluated in terms of thermal and surface charge properties, as well as in the microgel size and viscoelastic behavior. Finally, a preliminary study of the antimicrobial activity against different microorganisms is also performed in terms of minimum inhibitory concentration (MIC). From this study we determined that in contrast with butylated microgels, methylated ones show potential antimicrobial activity and good physical properties besides of maintaining microgel thermo-responsiveness.

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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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Effects of Peptide Secondary Structure on the Interaction with Oppositely Charged Microgels

Cited by 28 publications

References 47 publications

Drug-Induced Phase Separation in Polyelectrolyte Microgels

Drug-Induced Phase Separation in Polyelectrolyte Microgels

Thermoresponsive Poly(N-Isopropylacrylamide-co-Dimethylaminoethyl Methacrylate) Microgel Aqueous Dispersions with Potential Antimicrobial Properties

Factors Affecting Peptide Interactions with Surface-Bound Microgels

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