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Fibrin-enmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis
J Frucht-Perry1, K K Assil, E Ziegler
1Bethesda Eye Institute, Department of Ophthalmology, St. Louis University, MO 63110.
Abstract:
Treatment of bacterial keratitis requires frequent application of topical antibiotics. We studied the efficacy of a single topical administration of tobramycin incorporated in large multivesicular liposomes and enmeshed in a fibrin sealant on rabbit corneas infected with Pseudomonas aeruginosa. One cornea each of 25 New Zealand albino rabbits was infected with P. aeruginosa. Twenty-four hours later, the animals were randomly divided into five groups of five. Group A received single hourly drops (50 microliters) of fortified tobramycin (14.5 mg/ml, total of 17.4 mg). Group B received a single topical application of 3.5 mg tobramycin, in 0.1 ml multivesicular liposomes, enmeshed in a fibrin sealant with an overlaying bandage contact lens. Group C was treated in the same manner as group B without the addition of fibrin sealant. Groups D and E served as nondrug-treated controls, with group D receiving topical fibrin-enmeshed liposomes devoid of tobramycin and group E receiving hourly topical balanced salt solution (BSS) drops. All animals were killed 24 h after initiation of therapy. Significantly fewer colonies of Pseudomonas were present in corneas of all three treated groups, as compared with the two nondrug-treated control groups (p less than 0.02). There were significantly fewer colonies of Pseudomonas in groups A and B as compared with group C (p less than 0.02). No significant difference was noted between a single administration of topical fibrinen-meshed tobramycin-encapsulated liposomes (group B) and 24 doses of hourly fortified topical tobramycin (group A, p greater than 0.05). Tobramycin-encapsulated megaliposomes may serve as a useful adjunct in treatment of Pseudomonas keratitis.
Insights
A single dose of tobramycin in liposomes and fibrin sealant effectively treated Pseudomonas aeruginosa bacterial keratitis in rabbits, matching the efficacy of frequent antibiotic drops.
Area of Science:
- Ophthalmology
- Microbiology
- Drug Delivery Systems
Background:
- Bacterial keratitis, particularly Pseudomonas aeruginosa infections, necessitates frequent topical antibiotic application.
- Conventional treatments require multiple daily doses, impacting patient compliance and potentially leading to suboptimal outcomes.
- Novel drug delivery systems are needed to improve the efficacy and convenience of treating bacterial keratitis.
Purpose of the Study:
- To evaluate the efficacy of a single topical administration of tobramycin-loaded multivesicular liposomes within a fibrin sealant for treating Pseudomonas aeruginosa bacterial keratitis.
- To compare this novel formulation's effectiveness against conventional hourly fortified tobramycin drops and control treatments in a rabbit model.
Main Methods:
- New Zealand albino rabbits with experimentally induced Pseudomonas aeruginosa keratitis were used.
- Treatment groups included: hourly fortified tobramycin, single-dose tobramycin-liposomes-fibrin sealant, single-dose tobramycin-liposomes without fibrin, and two control groups (liposomes without drug, balanced salt solution).
- Bacterial colony counts in corneas were assessed 24 hours after treatment initiation.
Main Results:
- All tobramycin-treated groups showed significantly fewer Pseudomonas colonies compared to control groups.
- The single-dose tobramycin-liposomes-fibrin sealant group demonstrated efficacy comparable to multiple hourly doses of fortified tobramycin.
- The addition of fibrin sealant significantly enhanced the efficacy of tobramycin-liposomes compared to tobramycin-liposomes alone.
Conclusions:
- Single-dose topical tobramycin-encapsulated megaliposomes in fibrin sealant represent a promising alternative for treating Pseudomonas keratitis.
- This formulation may serve as a valuable adjunct, potentially improving treatment compliance and outcomes.
- Further research into liposomal drug delivery systems for ocular infections is warranted.
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