16β-methyl-17α,21-diesterified glucocorticoids as partial agonists of glucocorticoid in rat endotoxin-induced inflammation

Tsuji, Fumio; Sawa, Kenjiro; Mibu, Hiroyuki; Shirasawa, Eiichi

doi:10.1007/s000110050172

Cited by 4 publications

(3 citation statements)

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“…In rabbits and rats, PAF receptor antagonists suppressed anterior uveitis (13)(14)(15), but the effects of PAF antagonists on anterior uveitis in other species have not been examined. We have established a guinea pig EIU model, which showed a good correlation with that in humans in structure-activity relationship studies of glucocorticoids (17,19,20). The binding affinities of PAF to the PAF receptors are almost the same between man and guinea pigs in the lung (1).…”

Section: Discussionmentioning

confidence: 98%

The role of platelet-activating factor in cell infiltration in endotoxin-induced uveitis in guinea pigs

Tsuji

Shirasawa

1998

Current Eye Research

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Section: Discussionmentioning

confidence: 98%

The role of platelet-activating factor in cell infiltration in endotoxin-induced uveitis in guinea pigs

Tsuji

Shirasawa

1998

Current Eye Research

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“…Previous studies have revealed that systemic glucocorticoids such as dexamethasone (DEX) (9α-fluoro-16α-methyl-11β,17α,21-trihydroxy-1,4-pregnadiene-3,20-dione) mitigate the production of inflammatory mediators in EIU animal models [ 5 , 8 ]. DEX is a long-acting synthetic glucocorticoid and, among other corticosteroids, DEX sodium phosphate has the highest potency and efficacy against ocular inflammatory conditions [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Topical Sustained-Release Dexamethasone-Loaded Chitosan Nanoparticles: Assessment of Drug Delivery Efficiency in a Rabbit Model of Endotoxin-Induced Uveitis

Alkholief,

Kalam,

Raish

et al. 2023

Pharmaceutics

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Uveitis is an ocular illness that if not treated properly can lead to a total loss of vision. In this study, we evaluated the utility of HA-coated Dexamethasone-sodium-phosphate (DEX)-chitosan nanoparticles (CSNPs) coated with hyaluronic acid (HA) as a sustained ocular delivery vehicle for the treatment of endotoxin-induced-uveitis (EIU) in rabbits. The CSNPs were characterized for particle size, zeta potential, polydispersity, surface morphology, and physicochemical properties. Drug encapsulation, in vitro drug release, and transcorneal permeation were also evaluated. Finally, eye irritation, ocular pharmacokinetics, and pharmacodynamics were in vivo. The CSNPs ranged from 310.4 nm and 379.3 nm pre-(uncoated) and post-lyophilization (with HA-coated), respectively. The zeta potentials were +32 mV (uncoated) and −5 mV (HA-uncoated), while polydispersity was 0.178–0.427. Drug encapsulation and loading in the CSNPs were 73.56% and 6.94% (uncoated) and 71.07% and 5.54% (HA-coated), respectively. The in vitro DEX release over 12 h was 77.1% from the HA-coated and 74.2% from the uncoated NPs. The physicochemical properties of the CSNPs were stable over a 3-month period when stored at 25 °C. Around a 10-fold increased transcorneal-flux and permeability of DEX was found with HA-CSNPs compared to the DEX-aqueous solution (DEX-AqS), and the eye-irritation experiment indicated its ocular safety. After the ocular application of the CSNPs, DEX was detected in the aqueous humor (AH) till 24 h. The area under the concentrations curve (AUC0–24h) for DEX from the CSNPs was 1.87-fold (uncoated) and 2.36-fold (HA-coated) higher than DEX-AqS. The half-life (t1/2) of DEX from the uncoated and HA-coated NPs was 2.49-and 3.36-fold higher, and the ocular MRT0-inf was 2.47- and 3.15-fold greater, than that of DEX-AqS, respectively. The EIU rabbit model showed increased levels of MPO, TNF-α, and IL-6 in AH. Topical DEX-loaded CSNPs reduced MPO, TNF-α, and IL-6 levels as well as inhibited NF-κB expression. Our findings demonstrate that the DEX-CSNPs platform has improved the delivery properties and, hence, the promising anti-inflammatory effects on EIU in rabbits.

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“…We reported previously that the betamethasone derivative betamethasone dipropionate behaves as an antiglucocorticoid in rat endotoxin-induced uveitis (EIU) [5]. In addition, we reported that 16b-methyl-17a,21-diesterified glucocorticoids such as diflorasone diacetate, betamethasone dipropionate and beclomethasone dipropionate might act as partial glucocorticoid agonists in rat endotoxin-induced inflammation [6]. However, 16b-methyl-17a,21-diesterified glucocorticoids are potent topical glucocorticoids in man [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs

et al. 1997

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16β-methyl-17α,21-diesterified glucocorticoids as partial agonists of glucocorticoid in rat endotoxin-induced inflammation

Abstract: These results suggest that 16 beta-methyl-17 alpha,21-diesterified glucocorticoids might act as partial agonists of glucocorticoid in rats.

Cited by 4 publications

References 11 publications

The role of platelet-activating factor in cell infiltration in endotoxin-induced uveitis in guinea pigs

The role of platelet-activating factor in cell infiltration in endotoxin-induced uveitis in guinea pigs

Topical Sustained-Release Dexamethasone-Loaded Chitosan Nanoparticles: Assessment of Drug Delivery Efficiency in a Rabbit Model of Endotoxin-Induced Uveitis

The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs

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