Novel ophthalmic formulation of myriocin: implications in retinitis pigmentosa

Figures & data

Table 1. Composition (%, w/v) of unloaded NLC and Myr-NLC formulations.

	Gelucire 44/14	Mygliol 812	Tween 80	Benzalkonium chloride	Myr theoretical concentration (mg/ml)	Drug loading (mg/ml)*	% Encapsulation efficiency
NLC 0	10	5	2.5	0.05	–	–	–
NLC 1	10	5	2.5	0.05	1	0.68 ± 0.02	68.0
NLC 2	10	5	2.5	0.05	2	1.60 ± 0.003	80.0

*Drug loading was determined in three separate samples by means of HPLC-MS/MS.

Table 2. Characteristics of NLC formulations.

Batch	Z-Ave (nm)	PDI	ZP (mV)	Physical appearance	pH
NLC 0	86.25 ± 1.530	0.395 ± 0.006	3.81 ± 0.814	Clear	5.73
NLC 1	91.33 ± 3.153	0.658 ± 0.05	1.06 ± 0.179	Lightly milky	5.01
NLC 2	126.7±3.595	0.496 ± 0.002	2.48 ± 0.188	Milky	5.10

Table 3. Stability of NLC and Myr-NLC formulations.

	Z-Ave (nm)	PDI	pH	App
Time 0
NLC0	86.25 ± 1.530	0.395 ± 0.006	5.73	Clear
NLC1	91.33 ± 3.153	0.658 ± 0.050	5.01	Lightly milky
NLC2	126.70±3.595	0.496 ± 0.002	5.10	Milky
1 month
NLC0	93.58 ± 0.351	0.316 ± 0.034	5.56	Clear
NLC1	116.51 ± 0.833	0.273 ± 0.007	5.06	Lightly milky
NLC2	134.80 ± 2.06	0.380 ± 0.013	5.09	Milky
3 months
NLC0	102.31 ± 0.521	0.250 ± 0.001	5.55	Clear
NLC1	119.32 ± 1.570	0.244 ± 0.006	5.04	Lightly milky
NLC2	166.22 ± 5.781	0.474 ± 0.074	5.12	Milky
6 months
NLC0	134.90 ± 0.794	0.216 ± 0.022	5.58	Lightly milky
NLC1	122.22 ± 0.195	0.188 ± 0.015	5.20	Lightly milky
NLC2	189.99 ± 4.222	0.313 ± 0.111	5.31	Milky

Figure 1. Myriocin (topically administered as a myriocin-NLC) distribution in rabbit vitreous and retina. *p < .05 mouse retina vs. rabbit vitreous and retina. **p < .05 rabbit vitreous vs. rabbit retina.

Table 4. Ocular PK parameters of the myriocin-NLC (NLC1) formulation.

Tissue	Tmax (minutes)	Cmax (ng/g)	AUC0-204 (ng*min /g)
Mouse retina	240	2030061 ± 871475	80556900 ± 9611659*†
Rabbit vitreous	240	10996 ± 745	810507 ± 80068*
Rabbit retina	180	1646 ± 240	142789 ± 14898*

*p < .05 AUC_0-240 rabbit vitreous vs. rabbit retina; †p < .001 mouse retina vs. rabbit vitreous/rabbit retina.

Figure 2. Ceramides (A) and dihydroceramides (B) levels in the retina after topical administration of the myriocin-NLC. Ceramide or dihydroceramide range in control animals is represented by two dotted lines. *p < .05 **p < .001 Myr-NLC rabbits vs. vehicle-treated group.