Hydrogel device for analgesic drugs with in-situ loading and polymerization

Grindy, Scott; Gil, Dmitry; Suhardi, Jeremy; Fan, Yingfang; Moore, Kenneth L.; Hugard, Shannon; Leape, Charlotte P.; Randolph, Mark A.; Muratoglu, Orhun K.; Oral, Ebru

doi:10.1016/j.jconrel.2023.07.022

Cited by 5 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study also revealed the potential of the synergistic use of an analgesic in combination with an antibiotic as a novel prophylactic approach to prevent PJI. The design of functional implants for the local sustained delivery of antibiotics, as well as the delivery of synergistic combinations of drugs, can be possible based on our work on polymeric drug delivery devices [ 86 – 89 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Sekar,

Gil,

Tierney

et al. 2024

J Transl Med

Self Cite

View full text Add to dashboard Cite

Background While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. Methods Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment. Results Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. Conclusion The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

show abstract

Section: Discussionmentioning

confidence: 99%

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Sekar,

Gil,

Tierney

et al. 2024

J Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our study also revealed the potential of the synergistic use of an analgesic in combination with an antibiotic as a novel prophylactic approach to prevent PJI. The design of functional implants for the local sustained delivery of antibiotics as well as the delivery of synergistic combinations of drugs can be possible based on our work on polymeric drug delivery devices (88)(89)(90)(91).…”

Section: Discussionmentioning

confidence: 99%

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Sekar,

Gil,

Tierney

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. Methods Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of S. aureus and S. epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6hr) and established (24hr) biofilms were grown on 316 stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, MBEC measurement for GS, gene expression of biofilm-associated genes, visualization by live/dead imaging, scanning electron microscopy, and bacterial membrane fluidity assessment. Results Gentamicin-ketorolac combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin-ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. Conclusion The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

show abstract

“…For example, Grindy and coworkers developed a polyethylene glycol-poly(lactic acid) hydrogel system for a sustained drug release. They found that altering the ratio of the hydrophilic polyethylene glycol to a hydrophobic poly(lactic acid) in the hydrogel, or crosslinking the polyethylene glycol and poly(lactic acid) chains, could modulate the kinetics of drug release to maximize the therapeutic effect of the drug [192].…”

Section: Poly(lactic Acid)mentioning

confidence: 99%

Recent Advances in the Degradability and Applications of Tissue Adhesives Based on Biodegradable Polymers

Zhu,

Dou,

Zeng

et al. 2024

IJMS

View full text Add to dashboard Cite

In clinical practice, tissue adhesives have emerged as an alternative tool for wound treatments due to their advantages in ease of use, rapid application, less pain, and minimal tissue damage. Since most tissue adhesives are designed for internal use or wound treatments, the biodegradation of adhesives is important. To endow tissue adhesives with biodegradability, in the past few decades, various biodegradable polymers, either natural polymers (such as chitosan, hyaluronic acid, gelatin, chondroitin sulfate, starch, sodium alginate, glucans, pectin, functional proteins, and peptides) or synthetic polymers (such as poly(lactic acid), polyurethanes, polycaprolactone, and poly(lactic-co-glycolic acid)), have been utilized to develop novel biodegradable tissue adhesives. Incorporated biodegradable polymers are degraded in vivo with time under specific conditions, leading to the destruction of the structure and the further degradation of tissue adhesives. In this review, we first summarize the strategies of utilizing biodegradable polymers to develop tissue adhesives. Furthermore, we provide a symmetric overview of the biodegradable polymers used for tissue adhesives, with a specific focus on the degradability and applications of these tissue adhesives. Additionally, the challenges and perspectives of biodegradable polymer-based tissue adhesives are discussed. We expect that this review can provide new inspirations for the design of novel biodegradable tissue adhesives for biomedical applications.

show abstract

Hydrogel device for analgesic drugs with in-situ loading and polymerization

Cited by 5 publications

References 30 publications

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Recent Advances in the Degradability and Applications of Tissue Adhesives Based on Biodegradable Polymers

Contact Info

Product

Resources

About