Abstract
Purpose :
Conventional eye drops require high drug doses with multiple daily dosing to achieve efficacy due to rapid ocular clearance which leads to side effects and patient incompliance. This study tested the hypothesis that using mucoadhesive nanoparticle drug delivery platform (MyX-001) that specifically binds to ocular mucosa can lead to significant reduction in the required dose and dosage of Cyclosporin A (CsA), a dry eye therapeutic, in achieving therapeutic concentration.
Methods :
We evaluated the ocular pharmacokinetic properties of a single drop of CsA (0.02%) delivered via MyX-001 (MyX-CsA 0.02%) and compared it with a single application of market standard of care (SOC), an ointment with 0.2% CsA (SOC 0.2%) commonly used for treating dry eye in dogs. Three male New Zealand White rabbits were sacrificed for each group at each predefined timepoint after bilateral administration (n = 6 eyes). CsA concentration in cornea and conjunctiva (upper and lower combined) were analyzed using LC-MS. We also evaluated the ocular tissue concentration of CsA upon twice-a-week administrations of MyX-CsA 0.02%: one group dosed at day 1 (D1) and D3 while the other group was dosed at D1 and D4 and both were sacrificed on D7. Two-tailed student t-test (p < 0.05) was used for statistical analysis.
Results :
After a single dose administration, CsA tissue concentrations from MyX-CsA 0.02% showed significantly higher values, 479 ± 168 ng/g (2 hr) and 416 ± 119 ng/g (8 hr), compared to the ones after the SOC 0.2% administration (282 ± 103 ng/g and 260 ± 105 ng/g) despite having 10-fold less CsA concentration in each dose. In addition, CsA concentrations for MyX-CsA 0.02% showed that it was well within the theoretical effective concentration of CsA (50 to 300 ng/g) even 48 hrs after the initial dose but fell slightly below the threshold only after 144 hrs (Fig 1). Both twice-a-week dosing regimens showed that on D7, the CsA concentrations were well within the theoretical effective concentration range: D1 & D3 doses yielded 143 ± 43 ng/g and D1 & D4 doses 271 ± 106 ng/g on D7.
Conclusions :
The results are consistent with the hypothesis that drugs delivered using MyX-001, a non-invasive mucoadhesive nanoparticle platform, can significantly reduce the dose and dosage, down to once or twice a week to achieve therapeutically effective concentration in ocular tissues.
This is a 2020 ARVO Annual Meeting abstract.