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Daniel Hill, Claudia Sisa, Mariya Hristova, Satyanarayana Somavarapu, M Francesca Cordeiro; Gentamicin aided by Annexin to enhance crossing of biological barriers. Invest. Ophthalmol. Vis. Sci. 2020;61(7):407.
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Gentamicin does not easily cross biological barriers, such as the blood brain barrier and the blood retinal barrier, necessitating the use of high doses to achieve sufficient tissue penetration. Higher doses exacerbate the negative side effects associated with gentamicin, notably nephrotoxicity and inner ear damage. The aim of the present study was to investigate whether encapsulating gentamicin within annexin-functionalised liposomes (previously shown to cross biological barriers)1 would enhance the efficacy of intravenously administered gentamicin in a mouse model of meningitis.
Three groups of 10 female C57 8-week-old mice were infected intracisternally with P. aeruginosa. 2 hours post-infection, two groups received an intravenous a dose of gentamicin which was either unmodified or encapsulated in annexin-liposomes. The third group received empty annexin-liposomes. An additional group of 10 mice were left uninfected. Bodyweight and clinical condition (as a rating of 0 to 5) of animals were carried out 3 times per day, up to 48 hours post-infection, at which point brains were harvested, homogenised, and plated for CFU count.(Note, the clinical rating is as follows: 0-normal, 1-slight ruffled fur, 2-slight ruffled fur + reduced mobility, 3-ruffled fur + reduced mobility + rapid breathing, 4-ruffled fur + very reduced mobility + rapid breathing + huddled, 5-dead)
No statistical trends were noted for bodyweight or CFU data. A significant improvement in clinical score from vehicle control (mean rank = 19.25), to gentamicin (mean rank = 15.6), to encapsulated gentamicin (mean rank = 11.65) was demonstrated with the non-parametric Jonckheere-Terpstra test (p<0.02).
Encapsulation within annexin-liposomes appears to improve observed clinical reports of animal health and wellbeing. This supports the proposition that encapsulating gentamicin within functionalised liposomes enhances efficacy against P. aeruginosa meningitis, a result which may be mediated by enhanced crossing of the blood brain barrier, with potential applications to all biological barriers.Reference:1. Davis BM, Normando EM, Guo L, et al. Topical delivery of avastin to the posterior segment of the eye in vivo using annexin A5-associated liposomes. Small. 2014;10(8):1575-1584. doi:10.1002/smll.201303433
This is a 2020 ARVO Annual Meeting abstract.
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