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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 10/2011

01-10-2011 | Basic Science

Effect of menthol on ocular drug delivery

Authors: Xiaolin Xu, Nannan Yu, Zhengzhong Bai, Yanbin Xun, Di Jin, Zhijian Li, Hao Cui

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2011

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Abstract

Background

To assess how safe and effective it is to use menthol as a permeability enhancer in ophthalmic drug delivery systems.

Methods

In this study, the effect of menthol on permeability of dexamethasone disodium phosphate in the cornea and sclera was investigated in vitro. Application of topical drops and subconjunctival injection of dexamethasone disodium phosphate with or without 0.1% menthol was administered to rabbit eyes, and the drug concentration was detected in aqueous humor, cornea, vitreous, and retinochoroidal tissues. The safety of menthol was assessed on the basis of corneal hydration level, Draize test, electroretinography (ERG), and histological examination.

Results

0.05% and 0.1% menthol significantly enhanced the penetration of dexamethasone in the cornea, but did not change the dexamethasone penetration in sclera in vitro. When topical drops of dexamethasone containing 0.1% menthol were administered, a significantly increased concentration of dexamethasone in the cornea and aqueous humor tissues was reported, but dexamethasone concentrations remained unaffected in the retina–choroid tissues. On the other hand, increased drug concentration in aqueous humor, cornea, vitreous and retinochoroidal tissues was achieved through subconjunctival injection. No signs of irritation were observed when menthol was administered at concentrations ranging from 0.025%-0.1%; moreover, no substantial toxic reactions were observed in corneal hydration level, electrophysiological, or histological examinations after the addition of 0.1% menthol.

Conclusions

Menthol may improve the ocular penetration of a drug in a transcorneal and transscleral drug delivery system without causing toxic reactions.
Appendix
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Literature
1.
go back to reference Sultana Y, Jain R, Aqil M, Ali A (2006) Review of ocular drug delivery. Curr Drug Deliv 3(2):207–217PubMedCrossRef Sultana Y, Jain R, Aqil M, Ali A (2006) Review of ocular drug delivery. Curr Drug Deliv 3(2):207–217PubMedCrossRef
2.
go back to reference Hosoya K, Lee VH, Kim KJ (2005) Roles of the conjunctiva in ocular drug delivery: a review of conjunctival transport mechanisms and their regulation. Eur J Pharm Biopharm 60(2):227–240PubMedCrossRef Hosoya K, Lee VH, Kim KJ (2005) Roles of the conjunctiva in ocular drug delivery: a review of conjunctival transport mechanisms and their regulation. Eur J Pharm Biopharm 60(2):227–240PubMedCrossRef
3.
go back to reference Cruysberg LP, Nuijts RM, Geroski DH, Koole LH, Hendrikse F, Edelhauser HF (2002) In vitro human scleral permeability of fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein and rhodamine 6 G and the use of a coated coil as a new drug delivery system. J Ocul Pharmacol Ther 18(6):559–569PubMedCrossRef Cruysberg LP, Nuijts RM, Geroski DH, Koole LH, Hendrikse F, Edelhauser HF (2002) In vitro human scleral permeability of fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein and rhodamine 6 G and the use of a coated coil as a new drug delivery system. J Ocul Pharmacol Ther 18(6):559–569PubMedCrossRef
4.
go back to reference Bernatchez SF, Tabatabay C, Gurny R (1993) Sodium hyaluronate 0.25% used as a vehicle increases the bioavailability of topically administered gentamicin. Graefes Arch Clin Exp Ophthalmol 231(3):157–161PubMedCrossRef Bernatchez SF, Tabatabay C, Gurny R (1993) Sodium hyaluronate 0.25% used as a vehicle increases the bioavailability of topically administered gentamicin. Graefes Arch Clin Exp Ophthalmol 231(3):157–161PubMedCrossRef
5.
go back to reference Li X, Pan W, Ju C, Liu Z, Pan H, Zhang H, Nie S (2009) Evaluation of pharmasolve corneal permeability enhancement and its irritation on rabbit eyes. Drug Deliv 16(4):224–229PubMedCrossRef Li X, Pan W, Ju C, Liu Z, Pan H, Zhang H, Nie S (2009) Evaluation of pharmasolve corneal permeability enhancement and its irritation on rabbit eyes. Drug Deliv 16(4):224–229PubMedCrossRef
6.
go back to reference Maitani Y, Shimada K, Nagai T (1996) l-Menthol, oleic acid and lauricidin in absorption enhancement of free and sodium salt of diclofenac using ethanol treated silicone membrane as model for skin. Chem Pharm Bull (Tokyo) 44(2):403–408 Maitani Y, Shimada K, Nagai T (1996) l-Menthol, oleic acid and lauricidin in absorption enhancement of free and sodium salt of diclofenac using ethanol treated silicone membrane as model for skin. Chem Pharm Bull (Tokyo) 44(2):403–408
7.
go back to reference Ho HO, Chen LC, Lin HM, Sheu MT (1998) Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system. J Control Release 51(2–3):301–311PubMedCrossRef Ho HO, Chen LC, Lin HM, Sheu MT (1998) Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system. J Control Release 51(2–3):301–311PubMedCrossRef
8.
go back to reference Krishnaiah YS, Satyanarayana V, Karthikeyan RS (2002) Penetration enhancing effect of menthol on the percutaneous flux of nicardipine hydrochloride through excised rat epidermis from hydroxypropyl cellulose gels. Pharm Dev Technol 7(3):305–315PubMedCrossRef Krishnaiah YS, Satyanarayana V, Karthikeyan RS (2002) Penetration enhancing effect of menthol on the percutaneous flux of nicardipine hydrochloride through excised rat epidermis from hydroxypropyl cellulose gels. Pharm Dev Technol 7(3):305–315PubMedCrossRef
9.
go back to reference Brain KR, Green DM, Dykes PJ, Marks R, Bola TS (2006) The role of menthol in skin penetration from topical formulations of ibuprofen 5% in vivo. Skin Pharmacol Physiol 19(1):17–21PubMedCrossRef Brain KR, Green DM, Dykes PJ, Marks R, Bola TS (2006) The role of menthol in skin penetration from topical formulations of ibuprofen 5% in vivo. Skin Pharmacol Physiol 19(1):17–21PubMedCrossRef
10.
go back to reference Xu W, Wang ZR (1995) Effect of menthol and borneol on the distribution of sulfadiazine sodium and Evan’s blue in the rat and mouse brain. Pharmacol Clin Chin Mater Clin Med 6:31–33 Xu W, Wang ZR (1995) Effect of menthol and borneol on the distribution of sulfadiazine sodium and Evan’s blue in the rat and mouse brain. Pharmacol Clin Chin Mater Clin Med 6:31–33
11.
go back to reference Sun YM (2006) A few nonionic surfactants which are suited to ophthalmic drugs by comparing in the increased solubilization of the menthol. Qilu Pharmaceutical Affairs 25(3):171–172 [in Chinese] Sun YM (2006) A few nonionic surfactants which are suited to ophthalmic drugs by comparing in the increased solubilization of the menthol. Qilu Pharmaceutical Affairs 25(3):171–172 [in Chinese]
12.
go back to reference Eljarrat-Binstock E, Raiskup F, Frucht-Pery J, Domb AJ (2005) Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel. J Control Release 106(3):386–390PubMedCrossRef Eljarrat-Binstock E, Raiskup F, Frucht-Pery J, Domb AJ (2005) Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel. J Control Release 106(3):386–390PubMedCrossRef
13.
go back to reference Draize JH, Woodard G, Calvery HO (1944) Methods for the study of irritation and toxicity of substances. Pharmacol Exp Ther 82:377–390 Draize JH, Woodard G, Calvery HO (1944) Methods for the study of irritation and toxicity of substances. Pharmacol Exp Ther 82:377–390
14.
go back to reference Kao JC, Geroski DH, Edelhauser HF (2005) Transscleral permeability of fluorescent-labeled antibiotics. J Ocul Pharmacol Ther 21(1):1–10PubMedCrossRef Kao JC, Geroski DH, Edelhauser HF (2005) Transscleral permeability of fluorescent-labeled antibiotics. J Ocul Pharmacol Ther 21(1):1–10PubMedCrossRef
15.
go back to reference Eljarrat-Binstock E, Raiskup F, Stepensky D, Domb AJ, Frucht-Pery J (2004) Delivery of gentamicin to the rabbit eye by drug-loaded hydrogel iontophoresis. Invest Ophthalmol Vis Sci 45(8):2543–2548PubMedCrossRef Eljarrat-Binstock E, Raiskup F, Stepensky D, Domb AJ, Frucht-Pery J (2004) Delivery of gentamicin to the rabbit eye by drug-loaded hydrogel iontophoresis. Invest Ophthalmol Vis Sci 45(8):2543–2548PubMedCrossRef
16.
go back to reference Patel T, Ishiuji Y, Yosipovitch G (2007) Menthol: a refreshing look at this ancient compound. J Am Acad Dermatol 57(5):873–878PubMedCrossRef Patel T, Ishiuji Y, Yosipovitch G (2007) Menthol: a refreshing look at this ancient compound. J Am Acad Dermatol 57(5):873–878PubMedCrossRef
17.
go back to reference Del Amo EM, Urtti A (2008) Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today 13(3–4):135–143PubMed Del Amo EM, Urtti A (2008) Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today 13(3–4):135–143PubMed
18.
go back to reference Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC (2002) Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology 109(10):1887–1891PubMedCrossRef Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC (2002) Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology 109(10):1887–1891PubMedCrossRef
19.
go back to reference Kunta JR, Goskonda VR, Brotherton HO, Khan MA, Reddy IK (1997) Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin. J Pharm Sci 86(12):1369–1373PubMedCrossRef Kunta JR, Goskonda VR, Brotherton HO, Khan MA, Reddy IK (1997) Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin. J Pharm Sci 86(12):1369–1373PubMedCrossRef
20.
go back to reference Kaplun-Frischoff Y, Touitou E (1997) Testosterone skin permeation enhancement by menthol through formation of eutectic with drug and interaction with skin lipids. J Pharm Sci 86(12):1394–1399PubMedCrossRef Kaplun-Frischoff Y, Touitou E (1997) Testosterone skin permeation enhancement by menthol through formation of eutectic with drug and interaction with skin lipids. J Pharm Sci 86(12):1394–1399PubMedCrossRef
21.
go back to reference Okabe K, Kimura H, Okabe J, Kato A, Shimizu H, Ueda T, Shimada S, Ogura Y (2005) Effect of benzalkonium chloride on transscleral drug delivery. Invest Ophthalmol Vis Sci 46(2):703–708PubMedCrossRef Okabe K, Kimura H, Okabe J, Kato A, Shimizu H, Ueda T, Shimada S, Ogura Y (2005) Effect of benzalkonium chloride on transscleral drug delivery. Invest Ophthalmol Vis Sci 46(2):703–708PubMedCrossRef
22.
go back to reference McGhee CN, Dean S, Danesh-Meyer H (2002) Locally administered ocular corticosteroids: benefits and risks. Drug Saf 25(1):33–55PubMedCrossRef McGhee CN, Dean S, Danesh-Meyer H (2002) Locally administered ocular corticosteroids: benefits and risks. Drug Saf 25(1):33–55PubMedCrossRef
23.
go back to reference Monti D, Chetoni P, Burgalassi S, Najarro M, Saettone MF (2002) Increased corneal hydration induced by potential ocular penetration enhancers: assessment by differential scanning calorimetry (DSC) and by desiccation. Int J Pharm 232(1–2):139–147PubMedCrossRef Monti D, Chetoni P, Burgalassi S, Najarro M, Saettone MF (2002) Increased corneal hydration induced by potential ocular penetration enhancers: assessment by differential scanning calorimetry (DSC) and by desiccation. Int J Pharm 232(1–2):139–147PubMedCrossRef
24.
go back to reference Zambito Y, Zaino C, Burchielli S, Carelli V, Serafini MF, Di Colo G (2007) Novel quaternary ammonium chitosan derivatives for the promotion of intraocular drug absorption. J Drug Deliv Sci Tech 17(1):19–24 Zambito Y, Zaino C, Burchielli S, Carelli V, Serafini MF, Di Colo G (2007) Novel quaternary ammonium chitosan derivatives for the promotion of intraocular drug absorption. J Drug Deliv Sci Tech 17(1):19–24
Metadata
Title
Effect of menthol on ocular drug delivery
Authors
Xiaolin Xu
Nannan Yu
Zhengzhong Bai
Yanbin Xun
Di Jin
Zhijian Li
Hao Cui
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2011
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-011-1703-z

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