Received: 18 November 2021; Published on-line: 30 April 2022
Ocular hypotensive efficacy of a new liposomal latanoprost formulation administered by different routes for experimental ocular hypertension
I. M. Mikheytseva 1, G. S. Grygorieva 2, N. V. Pasyechnikova 1, S. G. Kolomiichuk 1, T. I. Siroshtanenko 1, N. F. Konakhovych 2
1 SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine"; Odesa (Ukraine)
2 SI "Institute of Pharmacology and Toxicology of NAMS of Ukraine"; Kyiv (Ukraine)
TO CITE THIS ARTICLE: Mikheytseva IM, Grygorieva GS, Pasyechnikova NV, Kolomiichuk SG, Siroshtanenko TI, Konakhovych NF. Ocular hypotensive efficacy of a new liposomal latanoprost formulation administered by different routes for experimental ocular hypertension. J.ophthalmol.(Ukraine).2022;2:37-41. http://doi.org/10.31288/oftalmolzh202223741
Background: Prostaglandin analogs (e.g., latanoprost) are the first-line therapy for glaucoma. These medications, however, have a short antihypertensive effect due to low penetration of topical drug across the corneal epithelium, which causes the need for their daily application for a long time. Therefore, it is clinically and socially important to develop latanoprost medications with improved efficacy against ocular hypertension (OHT) and with improved patient compliance through the prolonged effect of latanoprost.
Purpose: To assess (a) changes in intraocular pressure (IOP) with time and (b) duration of hypotensive effect of a proprietary liposomal latanoprost formulation administered topically or by subconjunctival injection for experimental OHT.
Material and Methods: Twenty-one adult Chinchilla rabbits (age, 1 year; weight, 2.5 to 3.0 kg) were divided into three groups: group 1, animals with induced OHT, which was treated with topical liposomal latanoprost (n = 7); group 2, animals with induced OHT, which was treated with a single subconjunctival injection of liposomal latanoprost (n = 7); and group 3, untreated animals with induced OHT, (n = 7). OHT was induced by two 0.1-mL anterior chamber injections of 0.3% carbomer at 10 day intervals. A 0.1-ml subconjunctival injection of liposomal latanoprost formulation was applied immediately after formation of the model of OHT. Topical liposomal latanoprost (one drop per eye) was bilaterally applied at a dose of 1 drop per eye once daily in the evening. Follow-up duration was 10 weeks. IOP was measured in each group before and after OHT modeling. In addition, it was measured after subconjunctival injection of liposomal latanoprost or first application of topical liposomal latanoprost. Thereafter, IOP measurements were performed once a week. Statistica 5.5 (StatSoft, Tulsa, OK, USA) software was applied for statistical analysis. Non-parametric statistical tests for dependent and independent samples were used.
Results: We assessed the pharmacological efficacy and duration of hypotensive effect of a proprietary liposomal latanoprost formulation administered topically or by subconjunctival injection for experimental OHT in rabbits. After OHT modeling was performed, there was a persistent increase in IOP, with the IOP values being 51-65% higher than at baseline (р < 0.001). The IOP in animals with OHT treated daily with topical liposomal latanoprost was 30.5% lower than in untreated animals with OHT (р < 0.001). A single subconjunctival injection of the examined liposomal latanoprost formulation resulted in a 36.7% reduction in IOP compared to baseline (р ˂ 0.001), with the effect being as long as 10 weeks.
Conclusion: The current study demonstrated a statistically significant hypotensive effect of topical or subconjunctival injection treatment with the examined liposomal latanoprost formulation, with the effect of a single subconjunctival injection of the formulation being as long as 10 weeks.
Keywords: liposomal latanoprost formulation, experimental ocular hypertension, intraocular pressure
Conflict of Interest Statement. The authors declare no conflict of interest.
Funding Support. There are no external sources of funding.
1.Zavgorodnia NG, Pasyechnikova NV. [Primary glaucoma: A new look at an old problem]. Zaporizhzhia: Orbita-YUG; 2010. Russian.
2.Marquis RE, Whitson JT. Management of glaucoma: focus on pharmacological therapy. Drugs Aging. 2005;22(1):1-21.
3.Alekseev VN, Levko MA, Al-Gifari M. [Comparative assessment of the efficacy of prostaglandins in combination therapy for primary glaucoma]. Glaucoma. 2009;1:44-48. Russian.
4.Schwartz GF, Tan J, Kotak S. Hyperemia-associated costs of medication changes in glaucoma patients treated initially with prostaglandin analogs. J Ocul Pharmacol Ther. 2009 Dec;25(6):555-61.
5.Andrés-Guerrero V, Vicario-de-la-Torre M, Molina-Martínez IT. Comparison of the in vitro tolerance and in vivo efficacy of traditional timolol maleate eye drops versus new formulations with bioadhesive polymers. Invest Ophthalmol Vis Sci. 2011 Jun 1;52(6):3548-56.
6.Hodzhaiev NS, Chernykh VV, Trunov AN. [Immune and biochemical changes in patients with POAG in the presence of Glauprost F2α prostaglandin analog]. Klinicheskaia oftalmologiia. 2013;13(2):1–4. Russian.
7.Latanoprost. National Library of Medicine. National Center for Biotechnology Information. 2020-08-29.
8.Egorov EA. [Ophthalmology: a Textbook for Medical School Students]. Moscow: Geotar media;2010. Russian.
9.Robin AL, Novack GD, Covert DW, et al. Adherence in glaucoma: objective measurements of once-daily and adjunctive medication use. Am J Ophthalmol. 2007 Oct;144(4):533-40.
10.Stone JL, Robin AL, Novack GD, et al. An objective evaluation of eye drop instillation in patients with glaucoma. Arch Ophthalmol. 2009 Jun;127(6):732-6.
11.Progress in drug and vaccine delivery. Proceedings of International Conferences on Liposome Advances. London-Athens;1990-2018.
12.Ako-Adounvo A, Nagarval R, Oliveira L, et al. Recent patents on ophthalmic nanoformulations and therapeutic implications. Recent Pat Drug Deliv Formul. 2014;8(3):193-201.
13.Grygorieva GS, Krasnopolskii IuM. [Pharmacotherapeutic status of liposomes per se]. Farmakologiia i likarska toksikologiia. 2020;14(4):264-71. Ukrainian.
14.Fathalla D, Fouad E, Soliman G. Latanoprost niosomes as a sustained realease ocular delivery for the management of glaucoma. Drug Dev Ind Pharm. 2020 May;46(5):806-813.
15.Information Bulletin No. 44, based on Pat. of Ukraine №124,724 issued 03.11.2021. Method for treatment of rhegmatogenous retinal detachment complicated by choroidal detachment. Authors: Pylypenko OIa, Grygorieva GS, Krasnopolskii IuM, Konakhovych NF, Mykheitseva IM, Pasyechnikova NV, Prokhorov VV.
16.Kim HG, Park JW. Experimental chronic ocular hypertension by anterior chamber injection of 0.3 % carbomer solution in the rat. Clin Exp Ophthalmol. May-Jun 2013;41(4):404-12.
17.Wang YY. [Experimental study of carbomer glaucoma model in rabbits by injecting different location in anterior chamber]. Ophthalmol. 2009;45:91- 5. Chinese.
18.Diestelhorst M, Larsson LI, European-Canadian Latanoprost Fixed Combination Study. A 12-week, randomized, double-masked, multicenter study of the fixed combination of latanoprost and timolol in the evening versus the individual components. Ophthalmology. 2006;113(1):70–6.
19.US 2013/020216606 А1, Pub Date 22.08.2013. Venkatraman S., Natarajan J.V., Wong T., Yin Chaiang F.B. Liposomal formulation for ocular drug delivery.
20.Natarajan JV, Ang M, Darvitan A, et al. Nanomedicine for glaucoma: liposomes provide sustained release latanoprost in the eye. Int J Nanomedicine. 2012;7:123-31.
21.Natarajan JV, Chattopadhyay S, Ang M, et al. Sustained release of anti-glaucoma drug: Demonstration of efficacy of a liposomal formulation on rabbit eye. Plos One. 2011;6(9):e24513.