In Vitro-Controlled Release Delivery System for Hydrogen Sulfide Donor

Ali, Hatim; Opere, Catherine A.; Singh, Somnath

doi:10.1208/s12249-014-0117-8

Cited by 14 publications

(8 citation statements)

References 51 publications

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“…One obvious area of long-acting H 2 S donor formulations is ocular applications (glaucoma), given the fact that intraocular administration of various H 2 S donors is known to have a significant lowering effect on the intraocular pressure (Salvi et al, 2016;Huang et al, 2017). Ali et al (2014) at Teva Pharmaceuticals disclosed the preparation of a dozen sustained release H 2 S formulations (designated as "phase-sensitive smart polymer-based formulations") by dissolving NaHS in polymer solutions, prepared by dissolving polymers (consisting of either polylactide or polylactide coglycolide, containing free carboxylic acid or capped allyl ester end group) in a mixture of benzyl benzoate and benzyl alcohol. The polymers contained 0.8% w/v NaHS, had physiological osmolarity, and their pH was adjusted to 7.4.…”

Section: H 2 S-donating Polymers and Special Pharmaceutical Formentioning

confidence: 99%

“…They had a variable degree (6%-27%) of initial H 2 S release ("burst release"), followed by a steady release of H 2 S, which was tracked over a period of 72 hours. It was concluded that controlled release of H 2 S (suitable for ocular indications where subconjunctival or subcutaneous administration would be the possible delivery routes) was achieved as a proof-of-principle by many of the disclosed formulations (Ali et al, 2014).…”

Section: H 2 S-donating Polymers and Special Pharmaceutical Formentioning

confidence: 99%

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

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Section: H 2 S-donating Polymers and Special Pharmaceutical Formentioning

confidence: 99%

Section: H 2 S-donating Polymers and Special Pharmaceutical Formentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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“…Just as regular drugs, H 2 S-releasing prodrugs can be administered orally ( 192 , 196 , 259 ), intraperitoneally ( 243 ), topically ( 185 ), ocularly ( 10 ), and intravenously ( 243 ). The H 2 S-releasing prodrugs that reached clinical trials—ATB-346, IK-1001, GIC-1001, DBTS, and SG1002—are orally administered, with the exception of IK-1001.…”

Section: Development Status Of H 2 S Prodrugsmentioning

confidence: 99%

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon¹,

Morales²

2020

Antioxidants & Redox Signaling

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Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H 2 S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H 2 S/SS in blood and/or tissues, and are amenable to treatment by H 2 S supplementation, development of safe and efficacious H 2 S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S 8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ringsubstituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H 2 S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H 2 S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H 2 S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H 2 S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H 2 S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new ''supramolecular tuning'' paradigm. Antioxid. Redox Signal. 33, 1010-1045.

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“…28 It has been claimed that in lower concentrations this oil is just a little irritant to the eye and does not cause any tissue damage. 29,30 BB was also applied for the development of Verisome TM which is an ocular drug delivery technology. 31…”

Section: Oil Solubility Studymentioning

confidence: 99%

Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and in Vitro Bioassay

Mehrandish

Mirzaeei

2021

Adv Pharm Bull

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Purpose: The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug. Methods: The oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE). Results: F7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model. Conclusion: The extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.

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In Vitro-Controlled Release Delivery System for Hydrogen Sulfide Donor

Cited by 14 publications

References 51 publications

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and in Vitro Bioassay

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In Vitro-Controlled Release Delivery System for Hydrogen Sulfide Donor

Cited by 14 publications

References 51 publications

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and in Vitro Bioassay

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Product

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors