Liposome-encapsulated 3H-5FU in Rabbits

Overview

Journal Int Ophthalmol

Specialty Ophthalmology

Date 1989 Sep 1

PMID 2625385

Citations 4

Authors

P Fishman

G A Peyman

R Hendricks

S L Hui

Affiliations

Soon will be listed here.

Abstract

We compared the pharmacokinetics of liposome-encapsulated tritiated 5-fluorouracil (3H-5FU-Lipo) to 3H-5FU in buffered saline (3H-5FU-PBS) after subconjunctival or intravitreal injection into rabbit eyes. Liposomes were prepared using phosphatidylcholine, phosphatidic acid, and alpha-tocopherol. Following a unilateral subconjunctival injection of either 3H-5FU-Lipo or 3H-5FU-PBS, rabbits were sacrificed at 0.5, 1, 4, and 8 hours. Significantly higher (p less than 0.05) drug levels were achieved with the encapsulated drug in the vitreous at all four time points and in the aqueous at three of four time points. Following bilateral intravitreal injections of 500 micrograms of 5FU in 0.1 ml, as either 3H-5FU-Lipo or 3H-5FU-PBS injected rabbits were sacrificed at 0, 6, 12, 24, and 48 hours. Vitreal drug levels were significantly higher (p less than 0.05) with encapsulated drug at all time points from 6 hours on. At 48 hours, the vitreal level with the encapsulated drug was 578 +/- 0.23 micrograms/ml compared with 1.06 +/- 0.07 micrograms/ml for 3H-5FU-PBS.

Citing Articles

Ocular Drug, Gene and Cellular Delivery Systems and Advanced Therapy Medicinal Products.

Eldem T, Eldem B Turk J Ophthalmol. 2018; 48(3):132-141.

PMID: 29988818 PMC: 6032955. DOI: 10.4274/tjo.32458.

Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes.

Wiechens B, Neumann D, Grammer J, Pleyer U, Hedderich J, Duncker G Int Ophthalmol. 1999; 22(3):133-43.

PMID: 10548457 DOI: 10.1023/a:1006137100444.

Liposomes in drug delivery. Clinical, diagnostic and ophthalmic potential.

Gregoriadis G, Florence A Drugs. 1993; 45(1):15-28.

PMID: 7680982 DOI: 10.2165/00003495-199345010-00003.

Liposomes as carriers of cancer chemotherapy. Current status and future prospects.

Kim S Drugs. 1993; 46(4):618-38.

PMID: 7506649 DOI: 10.2165/00003495-199346040-00004.

References

Peyman G, Schulman J . Proliferative vitreoretinopathy and chemotherapeutic agents. Surv Ophthalmol. 1985; 29(6):434-42. DOI: 10.1016/0039-6257(85)90208-5. View

Blumenkranz M, Ophir A, CLAFLIN A, Hajek A . Fluorouracil for the treatment of massive periretinal proliferation. Am J Ophthalmol. 1982; 94(4):458-67. DOI: 10.1016/0002-9394(82)90239-2. View

Tremblay C, Barza M, Szoka F, Lahav M, Baum J . Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits. Invest Ophthalmol Vis Sci. 1985; 26(5):711-8. View

Peyman G, Greenberg D, Fishman G, Fiscella R, Thomas A . Evaluation of toxicity of intravitreal antineoplastic drugs. Ophthalmic Surg. 1984; 15(5):411-3. View

Kimelberg H, Tracy Jr T, Biddlecome S, BOURKE R . The effect of entrapment in liposomes on the in vivo distribution of [3H]methotrexate in a primate. Cancer Res. 1976; 36(8):2949-57. View

Case J, Peyman G, Barrada A, Hendricks R, Fiscella R, Hindi M . Clearance of intravitreal 3H-fluorouracil. Ophthalmic Surg. 1985; 16(6):378-81. View

Peyman G . Antibiotic administration in the treatment of bacterial endophthalmitis. II. Intravitreal injections. Surv Ophthalmol. 1977; 21(4):332, 339-46. View

Kulnig W, Binder S, Riss B, Skorpik C . Inhibition of experimental intraocular proliferation with intravitreous 5-fluouracil. A transmission electron-microscopic study in rabbits. Ophthalmologica. 1984; 188(4):248-58. DOI: 10.1159/000309371. View

Szoka Jr F, Papahadjopoulos D . Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci U S A. 1978; 75(9):4194-8. PMC: 336078. DOI: 10.1073/pnas.75.9.4194. View

10.

Rootman J, Tisdall J, Gudauskas G, Ostry A . Intraocular penetration of subconjunctivally administered 14C-fluorouracil in rabbits. Arch Ophthalmol. 1979; 97(12):2375-8. DOI: 10.1001/archopht.1979.01020020591019. View

11.

Fishman P, Peyman G, Lesar T . Intravitreal liposome-encapsulated gentamicin in a rabbit model. Prolonged therapeutic levels. Invest Ophthalmol Vis Sci. 1986; 27(7):1103-6. View

12.

Avni I, Belkin M, Hercberg A, Blumenthal M . Intravitreal 5-fluorouracil in the prevention of post-traumatic vitreous proliferation. Ophthalmologica. 1984; 188(1):5-8. DOI: 10.1159/000309337. View

13.

Gregoriadis G . Drug entrapment in liposomes. FEBS Lett. 1973; 36(3):292-6. DOI: 10.1016/0014-5793(73)80394-1. View

14.

Binder S, Riss B, Skorpik C, Kulnig W . Inhibition of experimental intraocular proliferation with intravitreal 5-fluouracil. Graefes Arch Clin Exp Ophthalmol. 1983; 221(3):126-9. DOI: 10.1007/BF02133851. View

15.

Kane A, Barza M, Baum J . Intravitreal injection of gentamicin in rabbits. Effect of inflammation and pigmentation on half-life and ocular distribution. Invest Ophthalmol Vis Sci. 1981; 20(5):593-7. View

16.

Barza M, Baum J, Szoka Jr F . Pharmacokinetics of subconjunctival liposome-encapsulated gentamicin in normal rabbit eyes. Invest Ophthalmol Vis Sci. 1984; 25(4):486-90. View

17.

Kaye S . Liposomes--problems and promise as selective drug carriers. Cancer Treat Rev. 1981; 8(1):27-50. DOI: 10.1016/s0305-7372(81)80004-7. View

18.

Nao-i N, Honda Y . Toxic effect of fluorouracil on the rabbit retina. Am J Ophthalmol. 1983; 96(5):641-3. DOI: 10.1016/s0002-9394(14)73422-1. View

19.

Szoka Jr F, Papahadjopoulos D . Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng. 1980; 9:467-508. DOI: 10.1146/annurev.bb.09.060180.002343. View