Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability

Abstract

Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3–4 nm) and Soluplus (52–59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen’s egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

Resveratrol-Loaded Hydrogel Contact Lenses with Antioxidant and Antibiofilm Performance

“…The permeability and retention capacity of resveratrol released from the most promising hydrogels and Proclear ® 1 day CLs were investigated using porcine eyes, which are the most similar to human eyes considering the globe size, corneal thickness, ratio of globe diameter to corneal length, presence of Bowman’s layer, sclera histology and collagen bundle organization [ 72 ]. As a control, a resveratrol concentrated solution (70 µg/mL in ethanol:water 10:90 v / v medium) was used.…”

Imprinted Contact Lenses for Ocular Administration of Antiviral Drugs

“…VACV did not significantly accumulate in the sclera, but passed through it. Higher flux values recorded for porcine sclera can be related to their smaller thickness (73.2 ± 2.7 µm) compared to that of bovine sclera (129.8 ± 14.7 µm) as experimentally measured [61]. The permeation coefficient (P app ) was estimated referring the flux to the drug concentration measured in the donor chamber at the end of the test.…”

“…Nevertheless, the accumulation of VACV in the bovine cornea was remarkable ( Figure 8 b), being well above 20 µg/cm 2 for the three formulations. Accumulation was also observed in the porcine cornea although at lower levels, which may, in part, be related to its lower thickness [ 61 ]. Drug accumulation in the porcine cornea showed a clear dependence on the concentration gradient that the formulation provided on the ocular surface; namely, MIP V1:12 and VACV solution favored the highest accumulations.…”

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

“…Moreover, the in situ gelling performance of Soluplus micelle formulations may provide prolonged retention time on the eye surface. Soluplus micelles also encapsulate progesterone, which has therapeutic potential against retinal degeneration, more efficiently than Pluronic micelles [126]. The hydrophobic core of Soluplus facilitates the assembly at much lower CMC and the micelles are more stable.…”

“…The hydrophobic core of Soluplus facilitates the assembly at much lower CMC and the micelles are more stable. Studies carried out with cornea and sclera ex vivo from different animal sources (rabbit, pig, cow) revealed the strong influence of the interspecies anatomic differences on the drug permeability results, which may have an impact on the predictions of the performance on human eyes (Figure 3) [126].…”