Improved Anti-Inflammatory Effects in Rabbit Eye Model Using Biodegradable Poly Beta-Amino Ester Nanoparticles of Triamcinolone Acetonide

Sabzevari, Araz; Adibkia, Khosro; Hashemi, Hassan; Geest, Bruno G. De; Mohsenzadeh, Navid; Atyabi, Fatemeh; Ghahremani, Mohammad Hossein; Khoshayand, Mohammad-Reza; Dinarvand, Rassoul

doi:10.1167/iovs.13-12296

Cited by 24 publications

(9 citation statements)

References 29 publications

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“…Interestingly, the number of immuno-positive nuclei in the peripheral cornea of the group treated with the TA-loaded PEG2- b -PLA1 micelles suspended in chitosan hydrogel (group IV) was very scarce ( Figure 5(D) ). These results are in agreement with previous reports which showed that mucoadhesive nanoparticles of TA had better anti-inflammatory effect in the rabbit eyes compared with the drug suspension (Sabzevari et al., 2013a ). The enhanced anti-inflammatory efficacy of TA micelles suspended in chitosan hydrogel compared to all other formulations could be attributed to several factors.…”

Section: Resultssupporting

confidence: 94%

“…The drug loading capacity observed in this study is higher than that observed for other drugs encapsulated into polymeric micelles, which typically falls in the range of 5–10% w/w (Kim et al., 2010 ; Shen et al., 2017 ). Other polymeric nanoparticle formulations, such as those of poly( D,L -lactide-co-glycolide) (PLGA) and poly β-amino ester showed low TA loading capacity in the range of ∼1–5% (Sabzevari et al., 2013a , b ). High drug loading capacity observed in this study is advantageous since it limits the needed amounts of carrier polymers, which in turn limits the unnecessary burden of degrading, metabolizing and excreting the polymers from the body (Shen et al., 2017 ).…”

Section: Resultsmentioning

confidence: 99%

“…TA concentration in the micellar solution was determined by a previously reported HPLC method (Sabzevari et al., 2013a ). An Agilent Technologies HP 1100 chromatography system having a quaternary pump, a UV-visible diode array detector and a HP Vectra computer equipped with the HP-Chemstation software was used.…”

Section: Methodsmentioning

confidence: 99%

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Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model

et al. 2020

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The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)-blockpoly(e-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG-b-PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG-b-PLA micelles, respectively. The drug loading capacity was in the range of 6-12% and 15-25% for PEG-b-PCL and PEG-b-PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5-and 10-fold after loading into PEG-b-PCL and PEG-b-PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG-b-PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG-b-PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG-b-PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.

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Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

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Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model

et al. 2020

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“…TA inhibits the expression of intraocular neovascularization and inflammation 18 , 19 . The evaluation of TA injection on PGE2, HIF-1α, and VEGF concentrations in the aqueous and vitreous humor showed that the concentration of HIF-1α in the aqueous humor decreased at 12 h after TA injection.…”

Section: Discussionmentioning

confidence: 99%

Increased angiogenic factors in the aqueous and vitreous humors after disinsertion of extraocular muscle and the effects of triamcinolone acetate injection

Kang

Song

2022

Sci Rep

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The four extraocular rectus muscles in the rabbits were disinserted for induction of anterior segment ischemia (ASI) and the changes in the concentrations of prostaglandin E2 (PGE2), hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF) in the aqueous and vitreous humor were evaluated. Disinsertion of four rectus muscles in rabbits was performed in the right eyes of rabbits (ASI group). The concentrations of PGE2, HIF-1α, and VEGF in the aqueous and vitreous humor were measured at 1, 3, 6, 12, and 24 h by ELISA. The concentrations were compared with those of the fellow eyes (contralateral group) and normal healthy eyes (control group). Subconjunctival injection of triamcinolone acetonide (TA) was administered and three cytokine concentrations in the aqueous humor and vitreous humor were measured at 12 h after TA injection. A total of 48 eyes from 28 rabbits were included. The concentrations of PGE2, HIF-1α, and VEGF in the aqueous humor in the ASI and contralateral groups were significantly higher than those in the control group (p < 0.05, all). The aqueous and vitreous humor concentrations of VEGF in eyes with simultaneous TA injection were significantly lower than were those in the ASI group (p = 0.02, all). The concentration of PGE2, HIF-1α, and VEGF in the aqueous humor was increased after induction of ASI and TA injection seems to be effective in inhibiting VEGF elevation in ASI.

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“…Topically administered dorzolamide hydrochloride and timolol maleate have been shown to significantly reduce IOP in rabbits more and with a longer sustained effect when loaded in hyaluronic acid-modified chitosan nanoparticles compared to a marketed free drug formulation (Table 2) [33]. Polymeric nanoparticles loaded with various corticosteroids and administered through multiple routes including intravenous, topical, and subconjunctival, have been demonstrated to effectively reduce inflammation in animal models of uveitis [34][35][36]. When administered intravenously, nanoparticles formed from a co-polymer of poly(lactic acid) (PLA) and PEG, loaded with betamethasone phosphate, could effective distribute to the eyes of rats with experimental autoimmune uveoretinitis and reduce inflammatory symptoms for up to 14 d (Table 2) [34].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Distribution of polymeric nanoparticles in the eye: implications in ocular disease therapy

et al. 2021

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Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.

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Improved Anti-Inflammatory Effects in Rabbit Eye Model Using Biodegradable Poly Beta-Amino Ester Nanoparticles of Triamcinolone Acetonide

Abstract: It can be concluded that polymeric nanoparticles of triamcinolone acetonide will provide as good an anti-inflammatory effect as the subconjunctival injection method and are better compared with other drug delivery systems.

Cited by 24 publications

References 29 publications

Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model

Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model

Increased angiogenic factors in the aqueous and vitreous humors after disinsertion of extraocular muscle and the effects of triamcinolone acetate injection

Distribution of polymeric nanoparticles in the eye: implications in ocular disease therapy

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