Dextrin–rhEGF conjugates as bioresponsive nanomedicines for wound repair

Hardwicke, Joseph; Ferguson, Elaine Lesley; Moseley, Ryan; Stephens, Philip J.; Thomas, David W.; Duncan, Ruth

doi:10.1016/j.jconrel.2008.07.023

Cited by 109 publications

(114 citation statements)

References 36 publications

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“…170 The latter is one of the most interesting advances in the field of polymerdrug conjugates and, in particular, the design of macromolecular systems to promote tissue regeneration. 173,174 Within this context and, in particular, tissue regeneration and ischaemic diseases, the research carried out considering the above-mentioned Apaf-1 inhibitors as bioactive agents could be enclosed. Poly-L-glutamic acid (PGA)-based conjugates were suggested as adequate platforms for the delivery of this first-in-class family of apoptosis inhibitors.…”

Section: Synthetic Inhibitors Of the Apaf-1-mediated Apoptosome Assemmentioning

confidence: 99%

Molecules that modulate Apaf‐1 activity

Pérez‐Payá

Orzáez

Mondragón

et al. 2011

Medicinal Research Reviews

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Programmed cell death, apoptosis, is a highly regulated cellular pathway, responsible for the elimination of cells in the organism that are no longer needed or extensively damaged. Defects in the regulation of apoptosis could be at the molecular basis of different diseases, either when it is insufficient or excessive. The formation of the macromolecular complex, apoptosome, is a key event in this pathway, which has also been defined as the intrinsic apoptosis pathway. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated apoptotic protease-activating factor (Apaf-1), dATP, and procaspase-9. Recent studies have produced a wealth of information about the regulation and functions of Apaf-1, but additional studies aimed at elucidating its role as a signaling device at the crosstalk between different signaling pathways are needed to take advantage for the development of modulators of apoptosis pathways and possible therapeutic applications.

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Section: Synthetic Inhibitors Of the Apaf-1-mediated Apoptosome Assemmentioning

confidence: 99%

Molecules that modulate Apaf‐1 activity

Pérez‐Payá

Orzáez

Mondragón

et al. 2011

Medicinal Research Reviews

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“…Cargill Inc. -São Paulo, Brazil) or paper and packaging industry (e.g. LD Davis Industries -PA, USA); dextrin stabilizes the peptide, protects it from proteases and constitutes itself a release system, as it degrades upon contact with the amylases present in wound tissue, releasing the peptide over time [21,22].…”

Section: Introductionmentioning

confidence: 99%

Improved burn wound healing by the antimicrobial peptide LLKKK18 released from conjugates with dextrin embedded in a carbopol gel

et al. 2015

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This work presents a newly developed formulation that holds great potential as a therapeutic approach for burn treatment. It is based on the sustained delivery of an antimicrobial peptide - LLKKK18 - from conjugates with dextrin, after degradation of dextrin backbone upon exposure to wound α-amylases. Conjugates were further embedded in Carbopol®, a commercially available hydrogel, suitable for topical administration and that provides a moist environment to the wound. Overall, we obtained an efficient, safe and non-expensive formulation that improves burn wound healing, maintains a moist environment within the wound, is easy to apply-and-remove, and has potential to prevent infection due to the presence of an antimicrobial peptide. Importantly, this is the first time the wound healing ability of LLKKK18 is demonstrated and that its main mechanisms of action are identified.

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“…Duncan et al [24] proposed the use of HA for protein conjugation in the Polymer Masked-Unmasked Protein Therapy (PUMPT) concept. The hypothesis is that conjugation of a biodegradable polymer to a biologically active protein can mask activity and enhance stability in the bloodstream, while subsequent recovery of the activity can be achieved by degradation of the polymer at the target site.…”

Section: Ha-protein Conjugatesmentioning

confidence: 99%

“…Figure 11. Schematic representation of different HA activation methods and the following conjugation to proteins: (A) random conjugation of amino groups of proteins to carboxylic groups of HA [24]; (B) Slight HA oxidation in the presence of periodate and conjugation of HA-ALD with N-terminal primary amine group of proteins [78,79]; (C) Modification of HA with an acetal spacer for selective conjugation to the N-terminal amino groups after hydrolysis to the active aldehyde of the polymer [65]; and (D) Coupling of amino glycerol to HA carboxylic groups and partial oxidation for selective N-terminal conjugation to proteins [82]. Yang and co-workers applied this chemistry for the site-specific modification of human growth hormone (hGH) and interferon-α (IFNα) [78,79].…”

Section: Ha-protein Conjugatesmentioning

confidence: 99%

Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

2014

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Hyaluronic acid (HA) has currently several therapeutic applications: in ophthalmology, osteoarthritis, wound healing, tissue regeneration, postoperative anti-adhesion and anesthetic medicine. In the last ten years, it has also been successfully investigated in the field of drug delivery, in the form of conjugates or hydrogel depot systems. HAylation, the covalent conjugation of HA to bioactive molecules, allows the overcoming of disadvantages associated with some pharmaceuticals, such as insolubility, instability and fast kidney clearance. These issues can be addressed also by covalent attachment of polyethylene glycol (PEGylation), but HA has the relevant advantages of biodegradability, high loading and specific targeting. In this review, the novel HA derivatives and the latest advances in HA-based drug delivery with a particular focus on the chemistry of conjugation will be discussed. Although, so far, there are no HA-drug conjugates on the market, several derivatives are presently under clinical investigation, and the promising results encourage further investigations and the exploitation of this versatile polysaccharide.

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Dextrin–rhEGF conjugates as bioresponsive nanomedicines for wound repair

Cited by 109 publications

References 36 publications

Molecules that modulate Apaf‐1 activity

Molecules that modulate Apaf‐1 activity

Improved burn wound healing by the antimicrobial peptide LLKKK18 released from conjugates with dextrin embedded in a carbopol gel

Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

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