The interactions between doxorubicin and amphiphilic and acidic β-sheet peptides towards drug delivery hydrogels

Zarzhitsky, Shlomo; Rapaport, Hanna

doi:10.1016/j.jcis.2011.04.091

Cited by 35 publications

(25 citation statements)

References 36 publications

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“…The total amount of DOX loaded in the micelles was calculated as the summation of cumulative amount of drug released from the micelles and the amount of drug remaining in the micelles after release. The amount of DOX released from micelles was measured with UV absorbance at 232 nm . To determine the amount of drug retained in the micelles, the micelle suspension after drug release was freeze‐dried and then dissolved in DMF and analyzed by UV absorbance at 497 nm.…”

Section: Methodsmentioning

confidence: 99%

Fabrication of thermoresponsive, core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Chang

Hong

Zhang

et al. 2014

J of Applied Polymer Sci

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Thermoresponsive amphiphilic copolymer, poly[N-isopropyl acrylamide-co-3-(trimethoxysilyl)propylmethacrylate]-bpoly{N- [3-(dimethylamino)propyl]methacrylamide} with a branched structure was designed and synthesized by consecutive reversible addition-fragmentation chain-transfer polymerization. The further hydrolysis of trimethoxysilyl functions in 3-(trimethoxysilyl) propyl methacrylate units led to the fabrication of core-crosslinked (CCL) micelles with silica crosslinks at temperatures above the lower critical solution temperature of the poly(N-isopropyl acrylamide) block. The thermally induced structural and morphological changes of the CCL micelles in aqueous solution were investigated by transmission electron microscopy and 1 H-NMR analyses. The resulting CCL micelles were further explored as nanocarriers for the codelivery of an anticancer drug and nucleic acid for enhanced therapeutic efficacy. The CCL micelles effectively condensed the nucleic acid and mediated higher gene transfer in the presence of serum than in serum-free transduction. A cytotoxicity study revealed that whereas the pure CCL micelles exhibited unapparent cytotoxicity, the codelivery of p53 and doxorubicin with the CCL micelle formulation resulted in better treatment efficiency than sole chemotherapy.

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Section: Methodsmentioning

confidence: 99%

Fabrication of thermoresponsive, core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Chang

Hong

Zhang

et al. 2014

J of Applied Polymer Sci

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“…Self-assembled peptide-based hydrogels thus correspond to an important class of biomaterials that find application in tissue engineering and drug delivery. [20][21][22][23][24][25][26][27][28][29] The KLD12 peptide (Ac-KLDLKLDLKLDL) with its alternating ionic hydrophilic and hydrophobic amino acids was previously reported to spontaneously form stable β-sheet structures in aqueous solution. [30,31] Tung and co-workers described the design of a KLD12-based protease-sensitive hydrogel matrix containing a protease-cleavable region inserted between the KLD12 self-assembly motifs.…”

Section: Introductionmentioning

confidence: 99%

Controlled release of doxorubicin and Smac‐derived pro‐apoptotic peptide from self‐assembled KLD‐based peptide hydrogels

Yishay-Safranchik

Golan

David

2014

Polymers for Advanced Techs

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Self-assembled peptide hydrogels comprise an important class of biomaterials that find application in tissue engineering and drug delivery. We have developed injectable in situ-forming hydrogel formulations based on selfassembled KLD motifs to control the delivery of a conventional cytotoxic drug (doxorubicin [DOX]) or a Smac-derived pro-apoptotic peptide (SDPP) for cancer therapy. The core KLD peptide ([KLDL] 3 ) was separated into two β-sheet peptides by a three or four glycine-containing spacer (designated as 3G or 4G, respectively) or by a spacer containing four glycines and a phenylalanine (termed 4GF) to fine tune and influence the bulk properties. We found that the KLD-based hydrogel can effectively load DOX and SDPP within the hydrogel network. Addition of a three or four glycine-containing spacer arm decreased the time for gel formation, while inclusion of a single aromatic amino acid (F) into 4G sequence (4GF) significantly increased the rate of gel formation and improved its mechanical strength when compared to 3G-and 4G-containing gels. KLD16-and 4GF-based hydrogels presenting higher peptide concentrations can self-assemble very rapidly (in a few seconds) and were very effective at controlling the release of DOX and SDPP and inhibiting tumor cell growth in vitro. Pre-complexation of SDPP with polyanionic molecule (polyglutamic acid) further sustained in vitro drug release from 4GF-based formulations. This study is the first to test interactions between KLD-based hydrogel matrices and DOX or SDPP for local drug delivery applications.

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“…1,7,8,12 These self-assembled peptide matrices have been shown to function as drug delivery systems and as scaffolds that mimic extracellular matrices, useful for tissue regeneration purposes. [13][14][15][16] Gel formation requires inter-chain interactions that form junction points in molecular networks within solution that are strong enough and sufficiently abundant so as to impede the thermal motion of the solute molecules. The inclusion of solute molecules within the entanglement of the molecular network leads to the formation of supra-molecular solid-like structure able to resist external shear stresses.…”

Section: Introductionmentioning

confidence: 99%

The effect of pH and calcium ions on the stability of amphiphilic and anionic β‐sheet peptide hydrogels

et al. 2013

Self Cite

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Amphiphilic peptides can form bottom-up-designed self-assembled hydrogels composed of elongated fibril matrices that could find uses in various biologically-related systems, acting as platforms for drug delivery or scaffolds that mimic extracellular matrices in tissue regeneration systems. We have previously reported that the amphiphilic and anionic β-sheet forming peptide, Pro-Asp-(Phe-Asp)5 -Pro, P(FD)-5, generates hydrogels that template calcium-phosphate mineral and as such, were able to enhance bone formation in vivo. Our earlier results prompted us to further exploit the effects of pH and calcium ion concentration on P(FD)-5 peptide in solution, in hydrogels and in mineral-loaded hydrogel compositions. Circular dichroism-based characterization of solutions of the peptide demonstrated transitions between the unfolded state to a β-sheet structure as function of peptide concentration, pH and calcium ion concentration. FTIR measurements were employed to monitor differences between the structure of the peptide in solution and in hydrogels. Rheology and dissolution studies demonstrated the improved stability of hydrogels prepared by a two-step procedure, where the peptides are dissolved and self-assemble in the first step, while in the second step, calcium ions are allowed to adsorb onto the system. These results, highlighting the effects of a few central factors on the structure, assembly and stability of amphiphilic and anionic β-sheet peptide systems, will contribute to the further development of designed self-assembled peptide systems from solutions to hydrogels and hydrogel-loaded matrices, such as mineral putty compositions.

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The interactions between doxorubicin and amphiphilic and acidic β-sheet peptides towards drug delivery hydrogels

Cited by 35 publications

References 36 publications

Fabrication of thermoresponsive, core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Fabrication of thermoresponsive, core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Controlled release of doxorubicin and Smac‐derived pro‐apoptotic peptide from self‐assembled KLD‐based peptide hydrogels

The effect of pH and calcium ions on the stability of amphiphilic and anionic β‐sheet peptide hydrogels

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