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

Abstract

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.

Recent Strategies for Ocular Drug Delivery: Promises and Challenges

“…The prepared micelles had good in-vitro characteristics (size: 176.80 ± 2.25 nm, drug loading: 15-25%, sustained drug release over a period of 1 week and 10-fold increase in drug aqueous solubility). Furthermore, the elaborated micellar hydrogel formulation resulted in complete disappearance of the corneal inflammatory signs in tested rabbits based on histopathological examination [9].…”

“…Cequa ® (cyclosporine-A 0.09%) is a unique nanomicellar formulation, that is a clear solution approved for clinical use. In another study, Safwat et al [9] prepared poly ethylene glycol-block-poly lactic acid nanomicelles containing triamcinolone acetonide. The selected formulations were dispersed into chitosan hydrogel to evaluate their anti-inflammatory potential in a carrageenan-induced ocular inflammatory rabbit model.…”

Considerations for Polymers Used in Ocular Drug Delivery

“…Several stimuli-responsive poloxamers have been evaluated, including PF-127 for topical delivery of a hydrophobic drug to the anterior segment for treatment of allergic conjunctivitis (160), PF-68 for delivery of ferulic acid (161) or enhancing solubility of gatifloxacin in contact lenses (162), and their combination for delivery of antifungals (163). Triamcinolone acetonide delivery with PEG-block-PCL and PEG-block-PLA micelles was also evaluated (164). Other types of polymeric micelles evaluated include amino-terminated PEG-block-PLA and HPMC for delivery of tacrolimus (165).…”

Diabetic eye: associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment

“…Drugloaded micelles formulated in chitosan dispersion prolonged drug release for more than 1 week. In vivo (rabbit) evaluation in an inflammatory disease model revealed that twice a day instillation of the micelle solution with or without chitosan was able to recover the normal corneal epithelium [127]. Inulin-based mucoadhesive micelles have been shown suitable for encapsulation of anti-inflammatory drugs adequate for macular edema treatment, such as dexamethasone, triamcinolone, and triamcinolone acetonide, enhancing drug permeability through corneal cells, which could be an alternative to intraocular injections [128].…”