Delving into the Latest Updates on Antimicrobial peptide series(DermaGen) with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

+ [2]

Target-

Action

enhancers

Mechanism

Cell membrane permeability enhancers

Therapeutic Areas

Immune System DiseasesCongenital DisordersOtorhinolaryngologic Diseases+ [1]

Active Indication-

Inactive Indication

Acute otitis externaDermatitis, Atopic

Originator Organization

DermaGen AB

Active Organization-

Inactive Organization

DermaGen AB

Dermagen, Inc.Pergamum AB

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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The primary objective of this study is to evaluate safety and tolerability of DPK-060 2% ear drops compared to placebo for DPK-060 ear drops in patients with acute external otitis. The secondary objectives are to evaluate clinical cure and microbiological growth following treatment with DPK-060 2% ear drops compared to placebo for DPK-060 ear drops.

Start Date01 Nov 2011

Sponsor / Collaborator

DermaGen AB

[+1]

NCT01522391

/ CompletedPhase 1/2

A Randomized, Double-blinded Placebo-controlled Study to Investigate Antimicrobial Efficacy and Safety Following Topical Application of DPK-060

The primary objective of this study was to evaluate microbial density in eczematous lesions during two weeks of twice daily therapy with the investigational product, DPK-060 1% ointment, compared with placebo in patients with atopic dermatitis. This randomized, double-blind, placebo-controlled part of the study was preceded with an open-label investigation in a small group of patients (n=5) treated with two applications of DPK-060 1% ointment per day for four days to assess safety, local tolerability and systemic absorption of DPK-060.
The secondary objectives were to evaluate severity of eczema and pruritus, to assess the tolerability and safety of the treatment and to assess the degree of systemic absorption of DPK-060 in blood on Day 7 and Day 21 in a sub-set of 10 patients.

Start Date01 Mar 2008

Sponsor / Collaborator

DermaGen AB

100 Clinical Results associated with Antimicrobial peptide series(DermaGen)

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100 Translational Medicine associated with Antimicrobial peptide series(DermaGen)

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100 Patents (Medical) associated with Antimicrobial peptide series(DermaGen)

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8

Literatures (Medical) associated with Antimicrobial peptide series(DermaGen)

01 Apr 2023·Macromolecular Bioscience

Dendritic Nanogels Directed Dual‐Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections

Article

Author: Hutchinson, Daniel J. ; Umerska, Anita ; Håkansson, Joakim ; Malkoch, Michael ; San Jacinto García, Jorge ; Mahlapuu, Margit ; Fan, Yanmiao ; Andrén, Oliver C. J. ; Lüchow, Mads ; Zhang, Yuning ; Qin, Liguo

AbstractAntimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK‐060, a human kininogen‐derived AMP. Once embedded into the poloxamer gel, DPK‐060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time‐kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti‐infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK‐060 at the wound site, all formulations display superior efficacy compared to DPK‐060 in solution.

01 Sep 2022·Colloids and Surfaces B: Biointerfaces

Design and pharmacodynamic evaluation of DPK-060 loaded Nanostructured lipid carrier embedded gel for dermal delivery: A novel approach in the treatment of atopic dermatitis

Article

Author: Thakkar, Hetal ; Misra, Ambikanandan ; Javia, Ankit

DPK-060 is a synthetic, 17 amino acid peptide, structurally derived from the human protein kininogen. DPK-060 mainly acts by membrane disruption mechanism, thus demonstrating strong broad-spectrum antimicrobial activity against both gram-positive and gram-negative microbes, including methicillin-resistant S. aureus (MRSA) in-vitro and in-vivo. Apart from its antimicrobial effect, DPK-060 also possesses anti-inflammatory activity. In addition, DPK-060 has demonstrated positive results in phase II clinical trials in atopic dermatitis (AD) patients; but was not statistically conclusive due to the instability of DPK-060 as a drug substance in the formulation. Thus, the present investigation was aimed to assess and compare the efficacy of DPK-060 nanostructured lipid (NLC) based gel with conventional formulations (free DPK-060 gel and lotion) in AD mice animal models. DPK-060 loaded NLCs were formulated by meltemulsification technique and loaded into Carbopol 934 P gel and characterized for various physicochemical parameters such as particle size, zeta-potential, shape and surface morphology, rheological parameters, in-vitro drug release, cytotoxicity, cellular uptake, ex-vivo skin permeation/deposition, in-vitro antimicrobial activity, and proteolytic stability studies. NLCs exhibited 85 % encapsulation with 6.7 % loading efficacy, a size, and zeta potential of 128.6 nm and -22.5 mv, respectively. Additionally, DPK-060 NLC gel demonstrated controlled release and a better permeation profile in comparison to free DPK-060 gel and lotion. A substantial reduction in pro-inflammatory cytokines levels and improvement in AD lesions was achieved by DPK-060 NLC gel compared to free DPK-060 gel and lotion-based formulations. The present study confirms that DPK-060 NLC gel-based formulation can be an effective, safe, and novel alternative for the treatment of AD.

01 Oct 2019·Journal of Colloid and Interface ScienceQ2 · CHEMISTRY

Degradable dendritic nanogels as carriers for antimicrobial peptides

Q2 · CHEMISTRY

Article

Author: Singh, Shalini ; Malmsten, Martin ; Davoudi, Mina ; Malkoch, Michael ; Schmidtchen, Artur ; Nordström, Randi ; Andrén, Oliver C J

In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of such systems, we here address effects of nanogel charge, cross-linking, and degradation on peptide loading/release, as well as consequences of these factors for lipid membrane interactions and antimicrobial effects. The DNGs were found to bind the AMPs LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW). For the smaller DPK-060 peptide, loading was found to increase with increasing nanogel charge density. For the larger LL-37, on the other hand, peptide loading was largely insensitive to nanogel charge density. In line with this, results on the secondary structure, as well as on the absence of stabilization from proteolytic degradation by the nanogels, show that the larger LL-37 is unable to enter into the interior of the nanogels. While 40-60% nanogel degradation occurred over 10 days, promoted at high ionic strength and lower cross-linking density/higher anionic charge content, peptide release at physiological ionic strength was substantially faster, and membrane destabilization not relying on nanogel degradation. Ellipsometry and liposome leakage experiments showed both free peptide and peptide/DNG complexes to cause membrane destabilization, indicated also by antimicrobial activities being comparable for nanogel-bound and free peptide. Finally, the DNGs were demonstrated to display low toxicity towards erythrocytes even at peptide concentrations of 100 µM.

100 Deals associated with Antimicrobial peptide series(DermaGen)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute otitis externa	Phase 2	Sweden	Pergamum AB	01 Nov 2011
Dermatitis, Atopic	Phase 2	Sweden	Dermagen, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01522391 (CTgov)	Phase 1/2	Dermatitis, Atopic	41	Placebo for DPK-060 ointment (Placebo for DPK-060 Ointment)	(rwahnoreyp) = ygyeypfwdl wubqqmwzot (mdgflzetss, jdlmlyuebu - vwdqndatre) View more	-	05 Dec 2018
				DPK-060 1% ointment (DPK-060 1% Ointment)	(rwahnoreyp) = jbihmyrkec wubqqmwzot (mdgflzetss, yywcfxhmou - sdkdlhhzna) View more
NCT01447017 (CTgov)	Phase 2	Acute otitis externa	69	DPK-060 (DPK-060 2% Ear Drops)	ilsvxnomdn(bzkqpirllv) = bwnhjphpgj njaqbiegnf (jjehymezbz, wyirxzblvk - tontttjock) View more	-	10 Dec 2013
				Placebo for DPK-060 ear drops (Placebo for DPK-060 Ear Drops)	ilsvxnomdn(bzkqpirllv) = nffzhljafo njaqbiegnf (jjehymezbz, dmvbrraalw - ldprwahwtt) View more

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Biosimilar

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