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Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line.
J Pharm Sci 2001; 90(10):1505-15JP

Abstract

The purpose of this study is to assess the permeability of acyclovir (ACV) prodrugs through the rabbit corneal cell line (SIRC) as well as the cornea, and characterize the SIRC cell line for transport and metabolism studies of ester prodrugs. Prodrug derivatization of an acycloguanosine antiviral agent, acyclovir, was employed to improve its permeability across the cornea. New Zealand albino rabbits were used as an animal model for corneal studies. The SIRC cell line grown on polyester membranes was used for transport of these prodrugs. SIRC cells grown on the membrane support for 10 days developed four to six layers of epithelial cells, and this is comparable to the normal rabbit corneal epithelial layer. Transport experiments were conducted across the rabbit cornea and confluent SIRC cells using side-by-side diffusion-cell apparatus. Enzymatic hydrolysis of these compounds was evaluated in SIRC cell lysates. Appropriate reversed phase HPLC method(s) were employed for quantitation of both the prodrug and ACV simultaneously. Corneal permeabilities of some of these prodrugs (Malonyl ACV and Acetyl ACV) were higher relative to ACV. The SIRC cell line permeability values of all the prodrugs were higher compared to that of the intact cornea. The total amount of ACV-prodrugs transported, i.e., unhydrolyzed prodrugs and regenerated ACV, across the SIRC cell line was more relative to ACV. Hydrolytic studies in the SIRC cell line homogenate demonstrated the bioreversion potential of the prodrugs and the presence of enzymes, particularly the cholinesterase in the SIRC cell line. It may be concluded that the SIRC cell line is leakier compared to the cornea. Keeping in mind the limitations, the SIRC cell line after further characterization may be used for transport and metabolism studies of ester prodrugs.

Authors+Show Affiliations

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, Missouri 64110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11745709

Citation

Tak, R V., et al. "Transport of Acyclovir Ester Prodrugs Through Rabbit Cornea and SIRC-rabbit Corneal Epithelial Cell Line." Journal of Pharmaceutical Sciences, vol. 90, no. 10, 2001, pp. 1505-15.
Tak RV, Pal D, Gao H, et al. Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line. J Pharm Sci. 2001;90(10):1505-15.
Tak, R. V., Pal, D., Gao, H., Dey, S., & Mitra, A. K. (2001). Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line. Journal of Pharmaceutical Sciences, 90(10), pp. 1505-15.
Tak RV, et al. Transport of Acyclovir Ester Prodrugs Through Rabbit Cornea and SIRC-rabbit Corneal Epithelial Cell Line. J Pharm Sci. 2001;90(10):1505-15. PubMed PMID: 11745709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line. AU - Tak,R V, AU - Pal,D, AU - Gao,H, AU - Dey,S, AU - Mitra,A K, PY - 2001/12/18/pubmed PY - 2002/3/15/medline PY - 2001/12/18/entrez SP - 1505 EP - 15 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 90 IS - 10 N2 - The purpose of this study is to assess the permeability of acyclovir (ACV) prodrugs through the rabbit corneal cell line (SIRC) as well as the cornea, and characterize the SIRC cell line for transport and metabolism studies of ester prodrugs. Prodrug derivatization of an acycloguanosine antiviral agent, acyclovir, was employed to improve its permeability across the cornea. New Zealand albino rabbits were used as an animal model for corneal studies. The SIRC cell line grown on polyester membranes was used for transport of these prodrugs. SIRC cells grown on the membrane support for 10 days developed four to six layers of epithelial cells, and this is comparable to the normal rabbit corneal epithelial layer. Transport experiments were conducted across the rabbit cornea and confluent SIRC cells using side-by-side diffusion-cell apparatus. Enzymatic hydrolysis of these compounds was evaluated in SIRC cell lysates. Appropriate reversed phase HPLC method(s) were employed for quantitation of both the prodrug and ACV simultaneously. Corneal permeabilities of some of these prodrugs (Malonyl ACV and Acetyl ACV) were higher relative to ACV. The SIRC cell line permeability values of all the prodrugs were higher compared to that of the intact cornea. The total amount of ACV-prodrugs transported, i.e., unhydrolyzed prodrugs and regenerated ACV, across the SIRC cell line was more relative to ACV. Hydrolytic studies in the SIRC cell line homogenate demonstrated the bioreversion potential of the prodrugs and the presence of enzymes, particularly the cholinesterase in the SIRC cell line. It may be concluded that the SIRC cell line is leakier compared to the cornea. Keeping in mind the limitations, the SIRC cell line after further characterization may be used for transport and metabolism studies of ester prodrugs. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/11745709/Transport_of_acyclovir_ester_prodrugs_through_rabbit_cornea_and_SIRC_rabbit_corneal_epithelial_cell_line_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(16)30836-X DB - PRIME DP - Unbound Medicine ER -