Facile one-pot multicomponent synthesis of peptoid based gelators as novel scaffolds for drug incorporation and pH-sensitive release

Sebastian, Sharol; Yadav, Eqvinshi; Bhardwaj, Priya; Maruthi, Mulaka; Kumar, Deepak; Gupta, Manoj K.

doi:10.1039/d3tb01527k

Cited by 9 publications

(6 citation statements)

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“…These forces were not sufficient to drive the formation of supramolecular hydrogels, likely due to the reduced flexibility and increased steric bulk of the peptoids relative to their corresponding peptide sequence . Low-molecular-weight tripeptoid “organo hydrogels” have been recently demonstrated to form using polar organic solvents such as dimethyl sulfoxide (DMSO) and methanol in combination with water . Given the range of phosphorylated L-, D-, and β-peptide hydrogels that form due to the kinetics of enzyme-instructed self-assembly, , we believed that gelation may be possible by using a predominantly peptoid molecule.…”

Section: Results and Discussionmentioning

confidence: 99%

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proofof-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-D-lysine-O-phospho-D-tyrosine peptoid-D-peptide formulation ((NPhe) 4 GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague−Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78−1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe) 4 GGGGk(AZT)y(p)-OH to Sprague−Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC 90 ) range (30−130 ng mL −1 ) for 35 days.

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Section: Results and Discussionmentioning

confidence: 99%

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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“…In contrast, organogels offer a wider range of solvent options and advantageous encapsulation capabilities for water-insoluble drugs compared to hydrogels. 27 Self-assembled organogels, with distinctive qualities like viscoelasticity and adjustable material characteristics, 28 have shown promise in various biomedical applications. 29−32 Specific synthetic nanomaterials, such as polymers, quantum dots, and metal nanoparticles, exhibit improved stability and greater mechanical resilience.…”

Section: T H Imentioning

confidence: 99%

“…In contrast, organogels offer a wider range of solvent options and advantageous encapsulation capabilities for water-insoluble drugs compared to hydrogels . Self-assembled organogels, with distinctive qualities like viscoelasticity and adjustable material characteristics, have shown promise in various biomedical applications. − Specific synthetic nanomaterials, such as polymers, quantum dots, and metal nanoparticles, exhibit improved stability and greater mechanical resilience. However, their potential for clinical use may face hindrances due to issues related to size and surface-dependent toxicity, reduced compatibility with biological systems, and in vivo accumulation when compared to natural materials. , Consequently, the development of nanomaterials using biomolecules emerges as a promising solution to address these challenges owing to their excellent biocompatibility and biodegradability. , Peptides and amino acids demonstrate remarkable self-assembly capabilities , and excellent biocompatibility .…”

Section: Introductionmentioning

confidence: 99%

Silver and Copper Nanoparticle-Loaded Self-Assembled Pseudo-Peptide Thiourea-Based Organic–Inorganic Hybrid Gel with Antibacterial and Superhydrophobic Properties for Antifouling Surfaces

Devi,

Singh,

Singh

et al. 2024

ACS Appl. Bio Mater.

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The escalating threat of antimicrobial resistance has become a global health crisis. Therefore, there is a rising momentum in developing biomaterials with self-sanitizing capabilities and inherent antibacterial properties. Despite their promising antimicrobial properties, metal nanoparticles (MNPs) have several disadvantages, including increased toxicity as the particle size decreases, leading to oxidative stress and DNA damage that need consideration. One solution is surface functionalization with biocompatible organic ligands, which can improve nanoparticle dispersibility, reduce aggregation, and enable targeted delivery to microbial cells. The existing research predominantly concentrates on the advancement of peptide-based hydrogels for coating materials to prevent bacterial infection, with limited exploration of developing surface coatings using organogels. Herein, we have synthesized organogel-based coatings doped with MNPs that can offer superior hydrophobicity, oleophobicity, and high stability that are not easily achievable with hydrogels. The self-assembled gels displayed distinct morphologies, as revealed by scanning electron microscopy and atomic force microscopy. The cross-linked matrix helps in the controlled and sustained release of MNPs at the site of bacterial infection. The synthesized self-assembled gel@MNPs exhibited excellent antibacterial properties against harmful bacteria such as Escherichia coli and Staphylococcus aureus and reduced bacterial viability up to 95% within 4 h. Cytotoxicity testing against metazoan cells demonstrated that the gels doped with MNPs were nontoxic (IC50 > 100 μM) to mammalian cells. Furthermore, in this study, we coated the organogel@MNPs on cotton fabric and tested it against Gram +ve and Gram −ve bacteria. Additionally, the developed cotton fabric exhibited superhydrophobic properties and developed a barrier that limits the interaction between bacteria and the surface, making it difficult for bacteria to adhere and colonize, which holds potential as a valuable resource for self-cleaning coatings.

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“…6 Peptoids have also been utilised in biomedical sciences, 7,8 among which protein recognition and antimicrobial/antifungal activity are two prominent examples. 9,10 Recently Sharol et al generated a small library of organogelators with which the antibiotic metronidazole could be encapsulated and released with significant activity against E. coli , 11 further demonstrating the potential of this research area. Peptoid materials research has yielded a diversity of function, ranging from novel anti-freeze materials 12 to anti-fouling coatings.…”

Section: Introductionmentioning

confidence: 99%

Martinoid: the peptoid martini force field

Swanson,

van Teijlingen,

Lau

et al. 2024

Phys. Chem. Chem. Phys.

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Facile one-pot multicomponent synthesis of peptoid based gelators as novel scaffolds for drug incorporation and pH-sensitive release

Abstract: Infections caused by bacteria are the primary cause of illness and death globally for which antibiotics serve as the most given medications. However, there are certain inherent problems in administering...

Cited by 9 publications

References 93 publications

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Silver and Copper Nanoparticle-Loaded Self-Assembled Pseudo-Peptide Thiourea-Based Organic–Inorganic Hybrid Gel with Antibacterial and Superhydrophobic Properties for Antifouling Surfaces

Martinoid: the peptoid martini force field

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