Polyethylene Glycol-Based Hydrogels for Controlled Release of the Antimicrobial Subtilosin for Prophylaxis of Bacterial Vaginosis

Rajan, Sujata Sundara; Cavera, Veronica L.; Zhu, Xiaoping; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

doi:10.1128/aac.02446-14

Cited by 27 publications

(6 citation statements)

References 64 publications

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“…In a model study with nisin and Micrococcus luteus , one of the most sensitive reference microorganisms, it was shown that the most effective inhibition occurs when an initial phase of fast release is followed by a phase of slow release in smaller quantities, just enough to control the remaining population [45]. While appropriate food-grade delivery systems are still under investigation, they are available for a variety of pharmaceutical applications [46].…”

Section: Bacteriocins: Applications Are Determined By the Functionsmentioning

confidence: 99%

Functions and emerging applications of bacteriocins

Chikindas

Weeks

Drider

et al. 2018

Current Opinion in Biotechnology

440

258

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Bacteriocins, defined as ribosomally synthesized antimicrobial peptides, have traditionally been used as food preservatives, either added or produced by starter cultures during fermentation. In-depth studies of a select few bacteriocins opened exiting new research fields and broadened the application of these antimicrobial peptides. The possibility of developing bacteriocins into next generation antibiotics, accompanied with the rapid development in genetics and nanotechnology, paves the way to even more fascinating applications such as novel carrier molecules (delivery systems) and the treatment of cancer. Also, some bacteriocins are found to regulate quorum sensing which suggests novel applications for this group of substances. While there is some interesting translational research on bacteriocins from Gram-negative bacteria, the majority of application-oriented studies are focused on bacteriocins from Gram-positive microorganisms, mostly lactic acid bacteria. The applications of bacteriocins are expanding from food to human health.

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Section: Bacteriocins: Applications Are Determined By the Functionsmentioning

confidence: 99%

Functions and emerging applications of bacteriocins

Chikindas

Weeks

Drider

et al. 2018

Current Opinion in Biotechnology

440

258

View full text Add to dashboard Cite

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“…Microbicide-loaded hydrogels have been studied for sustained vaginal drug delivery, since in some clinical trials the maintenance of therapeutic drug concentrations for a prolonged period is essential. Sundara et al demonstrated the potential application of subtilosin-containing polyethylene glycol hydrogels for BV prophylaxis [ 17 ]. The hydrogels displayed an initial rapid-release phase (24 h) followed by a slow, sustained-release phase.…”

Section: Introductionmentioning

confidence: 99%

Thermosensitive Bioadhesive Hydrogels Based on Poly(N-isopropylacrilamide) and Poly(methyl vinyl ether-alt-maleic anhydride) for the Controlled Release of Metronidazole in the Vaginal Environment

et al. 2021

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The development of thermosensitive bioadhesive hydrogels as multifunctional platforms for the controlled delivery of microbicides is a valuable contribution for the in situ treatment of vagina infections. In this work, novel semi-interpenetrating network (s-IPN) hydrogels were prepared by the entrapment of linear poly(methyl vinyl ether-alt-maleic anhydride) (PVME-MA) chains within crosslinked 3D structures of poly(N-isopropylacrylamide) (PNIPAAm). The multifunctional platforms were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermal techniques, rheological analysis, swelling kinetic measurements, and bioadhesion tests on porcine skin. The hydrogels exhibited an interconnected porous structure with defined boundaries. An elastic, solid-like behavior was predominant in all formulations. The swelling kinetics were strongly dependent on temperature (25 °C and 37 °C) and pH (7.4 and 4.5) conditions. The s-IPN with the highest content of PVME-MA displayed a significantly higher detachment force (0.413 ± 0.014 N) than the rest of the systems. The metronidazole loading in the s-IPN improved its bioadhesiveness. In vitro experiments showed a sustained release of the antibiotic molecules from the s-IPN up to 48 h (94%) in a medium simulating vaginal fluid, at 37 °C. The thermosensitive and bioadhesive PNIPAAm/PVME-MA systems showed a promising performance for the controlled release of metronidazole in the vaginal environment.

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“…Consequently, there is an increasing interest in exploring antibacterial surfaces, which not only prevent infection but also helps in circumventing antibacterial resistance. Biomaterials like gels and hydrogels, with unique capability to hold water, have immense potential in such applications. − …”

Section: Introductionmentioning

confidence: 99%

Broad-Spectrum Antibacterial Activity of Proteolytically Stable Self-Assembled αγ-Hybrid Peptide Gels

et al. 2018

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Bacterial infections pose a serious threat to mankind, and there is immense interest in the design and development of self-assembled peptide gels using ultrashort peptides for antibacterial applications. The peptide gels containing natural amino acids suffer from poor stability against proteolytic enzymes. Therefore, there is a need to design and develop peptide gels with improved stability against proteolytic enzymes. In the present work, we report the synthesis and characterization of α/γ hybrid peptides Boc-D-Phe-γ-L-Phe-PEA (NH007) and Boc-L-Phe-γ-L-Phe-PEA (NH009) to improve the proteolytic stability. Both of the dipeptides were found to self-assemble into gels in aqueous DMSO (3-5% w/v), and the self-assembly process was studied using FTIR and CD, which indicated antiparallel β-sheet formation with random coils in NH007 gels and random or unordered conformation in NH009. The rheological studies indicated viscoelastic characteristics for both gels; the storage modulus ( G') for NH007 and NH009 gels (3% w/v) was estimated as 0.2 and 0.5 MPa, higher than the loss modulus ( G''). Also, both gels demonstrated self-healing characteristics for six consecutive cycles when subjected to varying strains of 0.1 and 30% (200 s each). The peptide gels were incubated with a mocktail of proteolytic enzymes, proteinase K, pepsin, and chymotrypsin, and stability was monitored using RP HPLC. Up to 23 and 40% degradation was observed for NH007 (3%, w/v) in 24 and 36 h, and 77 and 94% degradation was observed for NH009 (3%, w/v), within the same period. Thus α/γ hybrid peptide gels containing D-Phe exhibited higher stability than gels fabricated using L-Phe. The use of D-residue in α/γ hybrid peptide significantly enhanced the stability of peptides against proteolytic enzymes, as the stability data reported in this work are possibly the best in class. Both peptide gels exhibited broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria, such as Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. The Pseudomonas aeruginosa and Staphylococcus aureus, in particular, are known to develop resistance. The NH007 (3%, w/v) demonstrated 65% inhibition, whereas NH009 (3%, w/v) showed 78% inhibition, with potent activity against Pseudomonas aeruginosa. Mechanistic studies, using SEM, HR-TEM, and bacterial live-dead assay, indicated entrapment of bacteria in gel networks, followed by interaction with cell membrane components and lysis. Cell viability (MTT assay) and toxicity (LDH assay) studies showed that both gels are not toxic to NIH 3T3 mouse embryonic fibroblast cells (mammalian). MTT assay showed >85% cell viability, and LDH assay exhibited not more than 15% cytotoxicity, even at higher concentrations (5%, w/v) and prolonged exposures (48 h). Overall, studies indicate the potential application of gels developed from the α/γ hybrid peptides in preventing biomaterial-related infections.

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Polyethylene Glycol-Based Hydrogels for Controlled Release of the Antimicrobial Subtilosin for Prophylaxis of Bacterial Vaginosis

Cited by 27 publications

References 64 publications

Functions and emerging applications of bacteriocins

Functions and emerging applications of bacteriocins

Thermosensitive Bioadhesive Hydrogels Based on Poly(N-isopropylacrilamide) and Poly(methyl vinyl ether-alt-maleic anhydride) for the Controlled Release of Metronidazole in the Vaginal Environment

Broad-Spectrum Antibacterial Activity of Proteolytically Stable Self-Assembled αγ-Hybrid Peptide Gels

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