<scp>l</scp>-Carnosine: multifunctional dipeptide buffer for sustained-duration topical ophthalmic formulations

Singh, Sanjeet Kumar; Carreiro, Samantha; Chu, Jessie; Prasanna, Ganesh; Niesman, Michael R.; Collette, Walter; Younis, Husam S.; Sartnurak, Soisurin; Gukasyan, Hovhannes J.

doi:10.1211/jpp.61.06.0005

Cited by 16 publications

(2 citation statements)

References 37 publications

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“…Carnosine (β-alanyl-L-histidine), a naturally-occurring endogenous di-peptide, is present in surprisingly large amounts in long-lived human tissues. Numerous lines of evidence have pointed to the multi-functional significance of carnosine in the human body: (1) serves as a physiological buffering agent [30] , [116] , [117] and a metal ion (e.g., zinc and copper) chelator [118] – [120] ; (2) possessing anti-aging functions [121] , [122] , and free-radical scavenging activity [123] , [124] ; (3) capable of delaying senescence [125] and extending the life-span of cultured human fibroblasts [36] ; (4) able to kill transformed cells and protect cells against aldehydes and amyloid peptide fragment [126] . Other investigators have concluded that carnosine exhibits a well-documented anti-glycating activity against the glycation of proteins, including low-density lipoproteins, glucose degradation products, esterase, and histones [127] – [130] .…”

Section: Discussionmentioning

confidence: 99%

Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

Liu

How

et al. 2013

PLoS ONE

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Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

Liu

How

et al. 2013

PLoS ONE

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“…GG may either exist in its native form or upon alkaline hydrolysis originate the so called low-acyl GG [22], both forms retaining the capability to crosslink into hydrogels in the presence of mono-, di-and trivalent cations [24,25]. This polysaccharide has been proven suitable for the production of microbeads [26][27][28] or for the production of formulations for the sustained delivery of relevant drugs [29][30][31][32][33][34][35]. Due to its resemblance with the extracellular matrix glycosaminoglycan composition [36] it has gathered also important attention in the field of tissue engineering and regenerative medicine [37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems

et al. 2022

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Background T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efficacy and relatively weak side effects. Systems that optimize the stimulation of T cells to improve therapeutic efficacy are therefore in constant demand. A way to achieve this is through artificial antigen presenting cells that are complexes between vehicles and key molecules that target relevant T cell subpopulations, eliciting antigen-specific T cell priming. In such T cell activator systems, the vehicles chosen to deliver and present the key molecules to the targeted cell populations are of extreme importance. In this work, a new platform for the creation of T cell activator systems based on highly tailorable nanoparticles made from the natural polymer gellan gum (GG) was developed and validated. Methods GG nanoparticles were produced by a water in oil emulsion procedure, and characterized by dynamic light scattering, high resolution scanning electronic microscopy and water uptake. Their biocompatibility with cultured cells was assessed by a metabolic activity assay. Surface functionalization was performed with anti-CD3/CD28 antibodies via EDC/NHS or NeutrAvidin/Biotin linkage. Functionalized particles were tested for their capacity to stimulate CD4+ T cells and trigger T cell cytotoxic responses. Results Nanoparticles were approximately 150 nm in size, with a stable structure and no detectable cytotoxicity. Water uptake originated a weight gain of up to 3200%. The functional antibodies did efficiently bind to the nanoparticles, as confirmed by SDS-PAGE, which then targeted the desired CD4+ populations, as confirmed by confocal microscopy. The developed system presented a more sustained T cell activation over time when compared to commercial alternatives. Concurrently, the expression of higher levels of key cytotoxic pathway molecules granzyme B/perforin was induced, suggesting a greater cytotoxic potential for future application in adoptive cancer therapy. Conclusions Our results show that GG nanoparticles were successfully used as a highly tailorable T cell activator system platform capable of T cell expansion and re-education.

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Pharmaceutical Natural Polymers: Structure and Chemistry

Mogoşanu

Grumezescu

2015

Handbook of Polymers for Pharmaceutical Technologies

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l-Carnosine: multifunctional dipeptide buffer for sustained-duration topical ophthalmic formulations

Abstract: Functional synergy between excipients in gellan gum formulations buffered with l-carnosine has potential for topical ocular dosage forms with sustained precorneal residence.

Cited by 16 publications

References 37 publications

Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems

Pharmaceutical Natural Polymers: Structure and Chemistry

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