Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model

“…The major advantage of TAC-HβCD eye drops is that there is no need of using irritating excipients since our formulation strategy increases the solubilization of poorly soluble active ingredients and reduces the use of toxic products. In order to evaluate our formulation, a EIU model was selected because it is easily reproducible, quantifiable and clinical changes are similar to those of human acute uveitis [ 37 ]. Some authors stated that after LPS administration there is an activation of TLRs, increasing levels of proinflammatory mediators, developing inflammation of anterior uvea, choroid and retina and producing the breakdown of blood-humor barrier, with exudation of leukocytes into the aqueous humor [ 53 , 54 ].…”

“…In this regard, significantly lower levels of TNF-α, IL-6, MIP-1α and leukocytes, as well as histological evaluation of TAC-HPβCD compared to EIU group confirms the effectiveness of this formulation in the treatment of uveitis. Other authors stated that ophthalmic treatment with TAC solution in light mineral oil, a vehicle where this active substance is not adequately dissolved, was not able to improve any parameter related with clinical manifestation of uveitis comparing to a EIU model [ 37 ]. Consequently, our positive therapeutic effects using TAC-HPβCD demonstrate the proper solubilization of TAC in our formulation.…”

“…With respect to the limitations of our study, the fact that EIU model achieves the maximum inflammation 24 h after injection [ 36 , 37 ] makes necessary to carry out an accelerated dosage regimen and only permits a short-term evaluation which could constitute a hurdle regarding the translation of these results to the clinical setting. Another limitation is the lack of knowledge of the amount and rate of tacrolimus transcorneal permeation.…”

“…In the last decade, several formulations of TAC for topical ophthalmic administration have been synthetized, including niosomes [ 36 ], nanovesicles [ 37 ], micelles [ 38 ] and nanocapsules [ 39 ]. However, it is not possible their translation to clinical practice because their synthesis is very complex to be carried out in HPDs.…”

Ten Years of Knowledge of Nano-Carrier Based Drug Delivery Systems in Ophthalmology: Current Evidence, Challenges, and Future Prospective

“… Everolimus nanomicelles could be considered a promising topical drug delivery nanocarrier for treating uveitis. Garg V, et al 188 2021 Endotoxin-Induced Uveitis in Rabbit Tacrolimus Proglycosome nano-vesicles Propylene glycol modified lipid vesicles PNV treatment not only subsides clinical symptoms of uveitis but also prevents breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are a potential new topical treatment for uveitis.…”