Skye Bioscience Inc (SKYE)

[AntonChigurh]

INTRAOCULAR PRESSURE LOWERING EFFICACY
OF A ?9 -TETRAHYDROCANNABINOL PRODRUG, NB1111,
IN A NORMOTENSIVE RABBIT MODEL
P. Taskar1
, E. A. Ashour1
, W. Gul2
, M. A. ElSohly1,2 and S. Majumdar1
1
University of Mississippi, 2
ElSohly Laboratories, Inc., Mississippi, USA,
?9
-Tetrahydrocannabinol (THC), an active ingredient of the plant Cannabis sativa,
could potentially act as an anti-glaucoma agent. However due to its lipophilic nature,
THC does not permeate well across ocular tissues. NB1111 is a relatively hydrophilic
prodrug of THC with improved ocular bioavailability. The aim of this study was to
evaluate the effect of single and multiple day application of NB1111 loaded solid-lipid
nanoparticles (SLNs) on the intraocular pressure (IOP) of normotensive rabbits. IOP
lowering efficacy of a single application of NB1111-SLNs was also compared to that
of marketed ophthalmic formulations of pilocarpine and timolol maleate. NB1111 was
incorporated into SLNs, prepared by ultrasonication at concentrations of 0.98%. Fifty
microliters, of SLN or nanoemulsion, was instilled topically in the cul-de sac of the left
eye of normotensive rabbits (n=6), twice a day, for five consecutive days. For the single
day IOP-Time profiling, after the first application on Day 1, IOP was measured every
30 min till IOP returned to 90 % of the baseline. All animal studies were conducted
following UM IACUC approved protocols.
The data obtained on normotensive rabbits showed a significant IOP lowering effect by
NB1111 when formulated in SLNs. The maximum percent drop in the IOP from the
baseline IOP (?IOPmax) was 27.1%. The time for peak IOP reduction (Tmax), was 90
minutes and the duration of action for NB1111-SLN, or the time required for the ?IOP
to reach 90% of baseline IOP, was 480 minutes. The NB1111-nanoemulsion
formulation did not have a significant effect on the IOP of normotensive rabbits. The
?IOPmax was 11.7% and the Tmax was 60 minutes. The ocular concentrations obained
with the NB1111-nanoemulsion were also significantly lower than those obtained with
the NB1111-SLN formulation. The effect of THC-SLNs was also studied and it did not
have any effect on the IOP of normotensive rabbits. From the single dose studies, it was
observed that the marketed formulation, Pilocarpine HCl (2 %w/v) showed a ?IOPmax
of 15.9% at 30 minutes and its IOP lowering effect lasted for 120 minutes (Fig. 7).
Dosing with Timolol Maleate (0.25 % w/v) resulted in a more intense ?IOPmax of 23.1%
at 60 minutes with a duration of action of 180 minutes. The results show that NB1111-
SLN produced a significant increase in the intensity and duration of action, compared
to NB1111-nanoemulsion, THC-SLN, timolol and pilocarpine formulations;
demonstrating the positive effects of the vehicle, as well as the prodrug derivatization
of THC on the IOP lowering efficacy of THC.
Funded by: Nemus Bioscience Inc.

FROM ICRS2017