Intracorneal melatonin delivery using 2-hydroxypropyl-β-cyclodextrin ophthalmic solution for granular corneal dystrophy type 2

Jun Hyun Ahn, Hyun Do Kim, Sharif Md Abuzar, Ji Yeon Lee, Su Eon Jin, Eung Kweon Kim, Sung Joo Hwang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)608-616
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume529
Issue number1-2
DOIs
Publication statusPublished - 2017 Aug 30

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Ophthalmic Solutions
Cyclodextrins
Melatonin
Solubility
Corneal Stroma
Corneal Endothelium
Corneal Epithelium
Cornea
Corneal dystrophy Avellino type
Osmolar Concentration
Antioxidants
Rabbits

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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title = "Intracorneal melatonin delivery using 2-hydroxypropyl-β-cyclodextrin ophthalmic solution for granular corneal dystrophy type 2",
abstract = "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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Intracorneal melatonin delivery using 2-hydroxypropyl-β-cyclodextrin ophthalmic solution for granular corneal dystrophy type 2. / Ahn, Jun Hyun; Kim, Hyun Do; Abuzar, Sharif Md; Lee, Ji Yeon; Jin, Su Eon; Kim, Eung Kweon; Hwang, Sung Joo.

In: International Journal of Pharmaceutics, Vol. 529, No. 1-2, 30.08.2017, p. 608-616.

Research output: Contribution to journalArticle

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

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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