TY - JOUR
T1 - Intracorneal melatonin delivery using 2-hydroxypropyl-β-cyclodextrin ophthalmic solution for granular corneal dystrophy type 2
AU - Ahn, Jun Hyun
AU - Kim, Hyun Do
AU - Abuzar, Sharif Md
AU - Lee, Ji Yeon
AU - Jin, Su Eon
AU - Kim, Eung Kweon
AU - Hwang, Sung Joo
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/8/30
Y1 - 2017/8/30
N2 - Melatonin (MT), an effective antioxidant, has therapeutic implications for granular corneal dystrophy type 2 (GCD2) treatment. Eye drop formulations containing cyclodextrins (CDs) were studied with the objective of improving MT solubility, stability, and ocular absorption, while decreasing eye irritation. MT complexes with αCD, βCD, γCD, and 2-hydroxypropyl-βCD (HPβCD) were characterized by phase solubility studies, which demonstrated Higuchi's AL-type phase solubility profiles. The MT/HPβCD complex showed the highest MT solubility (2.75 mg/mL). Ocular irritation experiments showed HPβCD inclusion alleviated irritation of the eye. After administration of MT formulations to rabbit corneas, each harvested cornea was separated into corneal epithelium, stroma, and endothelium. MT concentrations in the corneal epithelium, stroma, and endothelium for the F1-treated group were 55.5 ± 9.24, 26.7 ± 2.66, and 21.1 ± 1.77 μM while those for the F2-treated group were 127.2 ± 21.01, 43.7 ± 16.93, and 51.0 ± 13.91 μM, respectively. Stability studies for 60 days showed no significant change in pH, osmolarity, and MT content. In conclusion, MT/HPβCD formulations can lower irritation, enhance MT stability, and improve therapeutic efficacy.
AB - Melatonin (MT), an effective antioxidant, has therapeutic implications for granular corneal dystrophy type 2 (GCD2) treatment. Eye drop formulations containing cyclodextrins (CDs) were studied with the objective of improving MT solubility, stability, and ocular absorption, while decreasing eye irritation. MT complexes with αCD, βCD, γCD, and 2-hydroxypropyl-βCD (HPβCD) were characterized by phase solubility studies, which demonstrated Higuchi's AL-type phase solubility profiles. The MT/HPβCD complex showed the highest MT solubility (2.75 mg/mL). Ocular irritation experiments showed HPβCD inclusion alleviated irritation of the eye. After administration of MT formulations to rabbit corneas, each harvested cornea was separated into corneal epithelium, stroma, and endothelium. MT concentrations in the corneal epithelium, stroma, and endothelium for the F1-treated group were 55.5 ± 9.24, 26.7 ± 2.66, and 21.1 ± 1.77 μM while those for the F2-treated group were 127.2 ± 21.01, 43.7 ± 16.93, and 51.0 ± 13.91 μM, respectively. Stability studies for 60 days showed no significant change in pH, osmolarity, and MT content. In conclusion, MT/HPβCD formulations can lower irritation, enhance MT stability, and improve therapeutic efficacy.
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U2 - 10.1016/j.ijpharm.2017.07.016
DO - 10.1016/j.ijpharm.2017.07.016
M3 - Article
C2 - 28694094
AN - SCOPUS:85025106925
SN - 0378-5173
VL - 529
SP - 608
EP - 616
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -