Nanoemulsions are liquid-in-liquid dispersion with a droplet size of about 100 nm. They have a transparent appearance, high rate of bioavailability, and increased shelf life. Nanoemulsions mainly consist of oil, water, surfactant, and cosurfactant and can be prepared by high- and low-energy methods. Diluted nanoemulsions are utilized for the delivery of ophthalmic drugs due to their capability to penetrate the deep layers of the ocular structure, provide a sustained release effect, and reduce the frequency of administration and side effects. These nanoemulsions are subjected to certain tests, such as safety, stability, pH profile, rheological studies, and so on. Cationic nanoemulsions are prepared for topical ophthalmic delivery of active ingredients from cationic agents to increase the drug residence time on the ocular surface, reducing their clearance from the ocular surface and improving drug bioavailability. This review article summarizes the main characteristics of nanoemulsions, ophthalmic nanoemulsions, and cationic nanoemulsions and their components, methods of preparation, and the evaluation parameters for ophthalmic nanoemulsions.
Nanoemülsiyonlar, yaklaşık 100 nm’lik bir damlacık boyutuna sahip sıvı içinde sıvı dispersiyonudur. Şeffaf bir görünüme, yüksek biyoyararlanıma ve artırılmış raf ömrüne sahiptirler. Nanoemülsiyonlar esas olarak yağ, su, yüzey aktif madde ve yardımcı yüzey aktif maddeden oluşur ve yüksek ve düşük enerjili yöntemlerle hazırlanabilir. Seyreltilmiş nanoemülsiyonlar, oküler yapının derin katmanlarına nüfuz etme, sürekli salım etkisi sağlama ve uygulama sıklığını ve yan etkileri azaltma kabiliyetleri nedeniyle oftalmik ilaçların verilmesi için kullanılır. Bu nanoemülsiyonlar, güvenlik, stabilite, pH profili, reolojik çalışmalar vb. gibi belirli testlere tabi tutulur. Katyonik nanoemülsiyonlar, ilacın oküler yüzey üzerinde kalış süresini artırmak, oküler yüzeyden klirensini azaltmak ve ilaç biyoyararlanımını geliştirmek için katyonik ajanlardan aktif bileşenlerin topikal olarak oftalmik taşınımı için hazırlanır. Bu derleme, nanoemülsiyonların, oftalmik nanoemülsiyonların ve katyonik nanoemülsiyonların temel özelliklerini ve bileşenlerini, hazırlama yöntemlerini ve oftalmik nanoemülsiyonlar için değerlendirme parametrelerini özetlemektedir.
1. Bucolo C, Drago F, Salomone S. Ocular drug delivery: a clue from nanotechnology. Front Pharmacol. 2012;3:1-3.
2. Al-bazzaz FY, Al-kotaji M. Ophthalmic in-situ sustained gel of ciprofloxacin, preparation and evaluation study. Int J Appl Pharm. 2018;10:153-161.
3. Ammar HO, Salama HA, Ghorab M, Mahmoud AA. Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride. AAPS PharmSciTech. 2009;10:808-819.
4. Kumari A, Sharma PK, Garg VK, Garg G. Ocular inserts: advancement in therapy of eye diseases. J Adv Pharm Technol Res. 2010;1:291-296.
5. Lallemand F, Daull P, Benita S, Buggage R, Garrigue JS. Successfully Improving Ocular Drug Delivery Using the Cationic Nanoemulsion, Novasorb. J Drug Deliv. 2012;2012:604204.
6. Shah J, Nair A, Jacob S, Patel R, Shah H, Shehata T, Morsy M. Nanoemulsion based vehicle for effective ocular delivery of moxifloxacin using experimental design and pharmacokinetic study in rabbits. Pharmaceutics. 2019;11:230.
7. SCCS. “Guidance on the safety assessment of nanomaterials in cosmetics”(2012). Avaialable from: https://ec.europa.eu/newsroom/ sante/items/661871
8. Yen CC, Chen YC, Wu MT, Wang CC, Wu YT. Nanoemulsion as a strategy for improving the oral bioavailability and antiinflammatory activity of andrographolide. Int J Nanomedicine. 2018;13:669-680.
9. Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol. 2013;2:47-64.
10. Huang D, Chen YS, Rupenthal ID. Overcoming ocular drug delivery barriers through the use of physical forces. Adv Drug Deliv Rev. 2018;126:96-112.
11. Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12:348-360.
12. Suri R, Beg S, Kohli K. Target strategies for drug delivery bypassing ocular barriers. J Drug Deliv Sci Technol. 2020;55:101389.
13. Singh V, Ahmad R, Heming T. The challenges of ophthalmic drug delivery: a review. Int J Drug Discov. 2011;3:56-62.
14. Agban Y, Thakur SS, Mugisho OO, Rupenthal ID. Depot formulations to sustain periocular drug delivery to the posterior eye segment. Drug Discov Today. 2019;24:1458-1469.
15. DeGorter MK, Xia CQ, Yang JJ, Kim RB. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol. 2012;52:249-273.
16. Ruponen M, Urtti A. Undefined role of mucus as a barrier in ocular drug delivery. Eur J Pharm Biopharm. 2015;96:442-446.
17. D’Emanuele A, Jevprasesphant R, Penny J, Attwood D. The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J Control Release. 2004; 95:447-453.
18. Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine. 2012;8:147-166.
19. Zdziennicka A, Krawczyk J, Szymczyk K, Jańczuk B. Macroscopic and microscopic properties of some surfactants and biosurfactants. Int J Molecular Sci. 2018;19:1934.
20. Čalija B. Microsized and nanosized carriers for nonsteroidal antiinflammatory drugs: formulation challenges and potential benefits. Belgrade: Academic Press; 2017.
21. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5:123.
22. Delmas T, Piraux H, Couffin AC, Texier I, Vinet F, Poulin P, Cates ME, Bibette J. How to prepare and stabilize very small nanoemulsions. Langmuir. 2011;27:1683-1692.
23. Park H, Han DW, Kim JW. Highly stable phase change material emulsions fabricated by interfacial assembly of amphiphilic block copolymers during phase inversion. Langmuir. 2015;31:2649-2654.
24. Ako-Adounvo AM, Nagarwal RC, Oliveira L, Boddu SHS, Wang XS, Dey S, Karla P. Recent Patents on ophthalmic nanoformulations and therapeutic implications. Recent Pat Drug Deliv Formul. 2014;8:193-201.
25. Subrizi A, del Amo EM, Korzhakov-Vlakh V, Tennikova T, Ruponen M, Urtti A. Design principles of ocular drug delivery systems: importance of drug payload, release rate, and material properties. Drug Discov Today. 2019;24:1446-1457.
26. Carli F, Baronian M, Schmid R, Chiellini E, inventors; AZAD Pharma AG, assignee. Ophthalmic oil-in-water emulsions containing prostaglandins. United States patent application. 2013; US 13/804,794.
27. Toris CB. Pharmacotherapies for glaucoma. Curr Mol Med. 2010;10:824- 840.
28. Khan W, Aldouby YH, Avramoff A, Domb AJ. Cyclosporin nanosphere formulation for ophthalmic administration. Int J Pharm. 2012;437:275- 276.
29. Benita S, Elbaz E, inventors; Yissum Research Development Co of Hebrew University, assignee. Oil-in-water emulsions of positively charged particles. United States patent US 6,007,826. 1999 Dec 28. Available from: https://patents.justia.com/assignee/yisum-researchdevelopment-company-of-the-hebrew-university-of-jerusalem
30. Wang B, Tian H, Xiang D. Stabilizing the oil-in-water emulsions using the mixtures of dendrobium officinale polysaccharides and gum arabic or propylene glycol alginate. Molecules. 2020;25:759.
31. Gupta A, Eral HB, Hatton TA, Doyle PS. Nanoemulsions: formation, properties and applications. Soft Matter. 2016;12:2826-2841.
32. Tadros TF. Emulsion formation, stability, and rheology. Emulsion formation and stability. 2013;1:1-75.
33. Qiu H, Chen X, Wei X, Liang J, Zhou D, Wang L. The emulsifying properties of hydrogenated rosin xylitol ester as a biomass surfactant for food: effect of ph and salts. Molecules. 2020;25:302.
34. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5:123.
35. Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech. 2007;8:E104.
36. Nikam TH, Patil MP, Patil SS, Vadnere GP, Lodhi S. Nanoemulsion: a brief review on development and application in parenteral drug delivery. Adv Pharm J. 2018;3:43-54.
37. Sharma N, Mishra S, Sharma S, Deshpande RD, Sharma RK. Preparation and optimization of nanoemulsions for targeting drug delivery. Int J Drug Dev Res. 2013;5:37-48.
38. Chávez-Zamudio R, Ochoa-Flores AA, Soto-Rodríguez I, Garcia-Varela R, García HS. Preparation, characterization and bioavailability by oral administration of O/W curcumin nanoemulsions stabilized with lysophosphatidylcholine. Food Funct. 2017;8:3346-3354.
39. Zhang J, Liu Z, Tao C, Lin X, Zhang M, Zeng L, Chen X, Song H. Cationic nanoemulsions with prolonged retention time as promising carriers for ophthalmic delivery of tacrolimus. Eur J Pharm Sci. 2020;144:105229.
40. Dukovski BJ, Juretić M, Bračko D, Randjelović D, Savić S, Moral MC, Diebold Y, Filipović-Grčić J, Pepić I, Lovrić J. Functional ibuprofenloaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. Int J Pharm. 2020;576:118979.
41. Kumar M, Bishnoi RS, Shukla AK, Jain CP. Techniques for Formulation of Nanoemulsion Drug Delivery System: A Review. Prev Nutr Food Sci. 2019;24:225-234.
42. Kotta S, Khan AW, Ansari SH, Sharma RK, Ali J. Formulation of nanoemulsion: a comparison between phase inversion composition method and high-pressure homogenization method. Drug Deliv. 2015;22:455-466.
43. Henostroza MA, Melo KJ, Yukuyama MN, Löbenberg R, Bou-Chacra NA. Cationic rifampicin nanoemulsion for the treatment of ocular tuberculosis. Colloids Surf A Physicochem Eng. 2020;597:124755.
44. Chime SA, Kenechukwu FC, Attama AA. Nanoemulsions-advances in formulation, characterization and applications in drug delivery. Intechopen: London; 2014.
45. Frank SG. Emulsions: Theory and Practice. In: Becher P, Wilmington, DE, eds. Partnership with American Chemical Society. (3rd ed). Oxford: Oxford University Press; 2001.
46. Hussain A, Altamimi MA, Alshehri S, Imam SS, Shakeel F, Singh SK. Novel approach for transdermal delivery of rifampicin to induce synergistic antimycobacterial effects against cutaneous and systemic tuberculosis using a cationic nanoemulsion gel. Int J Nanomedicine. 2020;15:1073.
47. Kulkarni SK. Nanotechnology: principles and practices. Switzerland: Springer; 2014.
48. Daull P, Feraille L, Elena PP, Garrigue JS. Comparison of the antiinflammatory effects of artificial tears in a rat model of corneal scraping. J Ocul Pharmacol Ther. 2016;32:109-118.
49. Dell SJ, Gaster RN, Barbarino SC, Cunningham DN. Prospective evaluation of intense pulsed light and meibomian gland expression efficacy on relieving signs and symptoms of dry eye disease due to meibomian gland dysfunction. Clin Ophthalmol. 2017;11:817-827.
50. Daull P, Lallemand F, Garrigue JS. Benefits of cetalkonium chloride cationic oil-in-water nanoemulsions for topical ophthalmic drug delivery. J Pharm Pharmacol. 2014;66:531-541.
51. Campbell PI. Toxicity of some charged lipids used in liposome preparations. Cytobios. 1983;37:21-26.
52. Manosroi A, Podjanasoonthon K, Manosroi J. Development of novel topical tranexamic acid liposome formulations. Int J Pharm. 2002;235:61- 70.
53. Draz MS, Fang BA, Zhang P, Hu Z, Gu S, Weng KC, Gray JW, Chen FF. Nanoparticle-Mediated Systemic Delivery of siRNA for Treatment of Cancers and Viral Infections. Theranostics. 2014;4:872-892.
54. Wu TH, Craven A, Tran T, Tran K, So K, Levi DM, Li RW. Enhancing coarse-to-fine stereo vision by perceptual learning: An asymmetric transfer across spatial frequency spectrum. Invest Ophthalmol Vis Sci. 2014;55:751.
55. Liu DX, Zhao XT, Liang W, Li JW. The stability and breakage of oil-in-water from polymer flooding produced water. Pet Sci Technol. 2013;31:2082- 2088.
56. Patel N, Nakrani H, Raval M, Sheth N. Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability. Drug Deliv. 2016;23:3712-3723.
57. Gurpreet K, Singh SK. Review of nanoemulsion formulation and characterization techniques. Indian J Pharm Sci. 2018;80:781-789.
58. Mahran A, Ismail S, Allam AA. Development of Triamcinolone AcetonideLoaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation. Pharmaceutics. 2021;13:444.
59. Salimi A. Preparation and evaluation of celecoxib nanoemulsion for ocular drug delivery. Asian J Pharm. 2017;11:543-550.
60. Mahboobian MM, Foroutan SM, Aboofazeli R. Brinzolamide-loaded nanoemulsions: in vitro release evaluation. Iran J Pharm Sci. 2016;12:75- 93.
61. Lallemand F, Schmitt M, Bourges JL, Gurny R, Benita S, Garrigue JS. Cyclosporine a delivery to the eye: a comprehensive review of academic and industrial efforts. Eur J Pharm Biopharm. 2017;117:14-28.
62. Sharif HR, Sharif MK, Zhong F. Preparation, characterization and rheological properties of vitamin E enriched nanoemulsion. Pak J Food Sci. 2017;27:7-14.
63. Sarı ES, Koç R, Yazıcı A, Şahin G, Çakmak H, Kocatürk T, SS Ermiş. Tear osmolarity, break-up time and schirmer’s scores in parkinson’s disease. Turk J Ophthalmol. 2015;45:142.
64. Gallarate M, Chirio D, Bussano R, Peira E, Battaglia L, Baratta F, Trotta M. Development of O/W nanoemulsions for ophthalmic administration of timolol. Int J Pharm. 2013;440:126-134.
65. Khan NU, Ali A, Khan H, Khan ZU, Ahmed Z. Stability Studies and Characterization of Glutathione-Loaded Nanoemulsion. Journal of cosmetic science. 2018;69:257-267.
66. Gupta A, Narsimhan V, Hatton TA, Doyle PS. Kinetics of the change in droplet size during nanoemulsion formation. Langmuir. 2016;32:11551- 11559.
67. Al-Omari NA, Butrus NH. Preparation, characterization and cytotoxic evaluation of novel au(iii) complexes of thioglycolate and 2-mercaptoglycolate ligands. Iraqi J Pharm Sci. 2013;13:28-40.
68. Rao R, Upadhyay SC, Singh MK. Nanoemulsion in ophthalmics: a newer paradigm for sustained drug delivery and bioavailability enhancement in ophthalmic manifestations. Int J Pharm Sci Rev Res. 2018;50:18-24.
69. Meng T, Kulkarni V, Simmers R, Brar V, Xu Q. Therapeutic implications of nanomedicine for ocular drug delivery. Drug Discov Today. 2019;24:1524- 1538.