Preparation and ex-vivo ocular delivery of Thermo-responsible pluronic F- 127 hydrogel containing propranolol hydrochloride- loaded Liposomes

Document Type : Research Paper

Authors

1 Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,Iran

2 School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences

3 Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences

4 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Poor bioavailability of ophthalmic drops is mainly due to rapid nasolacrimal drainage and eye impermeability of corneal epithelium. The main aim of this study is to prepare a liposomal hydrogel for the ocular delivery of propranolol hydrochloride as a β-blocker drug to enhance drug concentration at the desired site of action.
Materials and Methods: In this study liposome formulations were designed and prepared by homogenization and thin-layer methods and then dispersed into the pluronic based hydrogel. The optimized liposomes and liposomal hydrogel were used in Ex-vivo ocular permeation studies through the rabbit’s eye.
Results: liposomes showed 170-380 nm particle size, 34-65% entrapment efficiency, and sustained release profiles that 30-60 % of loaded drug released after 24 h. liposomes dispersed in hydrogels demonstrated a lower release rate. Liposomes and liposomal hydrogel increased ocular bioavailability of more than 3-folds.
Conclusion: In this study, the administration of thermo-responsible factors (pluronic) led to longer resistance time of the dosage form in the eye because the drug would turn into gel structures at the body temperature. Therefore, a system consisting of both pluronic factor and liposomes will be of great interest because it will pair up the Thermo gelling properties of the pluronic factor and the carrier characteristics of the liposome formulations.

Keywords


1.Pharmacotherapy Handbook. seventh ed: Mc Graw Hill; Cecily v. Dipiro.
2. Zimmerman TJ. Topical ophtalmic beta blockers: a comparative review. J Ocular Pharmacol. 1993; 9(4): 373-84.
3.Borthne A. the treatment of glucoma with propranolol: A clinical trial. Acta Ophthalmologica. 1976; 54 (3): 291-300.
4. Brooks AV, Gillies WE. Ocular β-Blockers in Glaucoma Management. Drugs & Aging. 1992; 2(3): 208-221.
5.Kaur IP, Garg A, Singla AK, Aggarwal D. Vesicular systems in ocular drug delivery: an overview. Int J Pharm. 2004; 269(1): 1-14.
6.Mishra GP, Bagui M, Tamboli V, Mitra AK. Recent applications of liposomes in ophthalmic drug delivery. J Drug Del. 2011; Article ID 863734  https://doi.org/10.1155/2011/863734.
7.Le Bourlais C, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems—Recent advances. Prog in Retinal and Eye Res. 1998; 17(1): 33-58.
8.Nagarsenker MS, Londhe VY, Nadkarni GD. Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery. Int J Pharm. 1999; 190(1): 63-71.
9.Aungst BJ. Absorption enhancers: applications and advances. AAPS J. 2012; 14(1): 10-18.
10.Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238-247.
11.Shek P, Barber R. Liposomes are effective carriers for the ocular delivery of prophylactics. Biochimica et Biophysica Acta (BBA)-Biomembranes. 1987;902(2):229-36.
12.Poznansky MJ, Juliano RL. Biological approaches to the controlled delivery of drugs: a critical review. Pharmacol Rev. 1984;36(4):277-336.
13.Feghhi M, Sharif Makhmalzadeh B, Farrahi F, Akmali M, Hasanvand N. Anti-microbial effect and in vivo ocular delivery of ciprofloxacin-loaded liposome through Rabbit’s eye. J Eye Res. 2020; Feb: doi.org/10.1080/02713683. 2020. 1728777.
14.Tan G, Yu S, Pan H, Li J, Liu D, Yuan K, Yang X, Pan W. Bioadhesive chitosan-loaded liposomes: A more efficient and higher permeable ocular delivery platform for timolol maleate. Int J Biol Macromol. 2017; 94: 355-363.
15.Takashima Y, Tsuchiya T, Igarashi Y, Kanazawa T, Okada H, Urtti A. Non-invasive ophthalmic liposomes for nucleic acid delivery to the posterior segment of eye. Yakugaku Zasshi: J of Pharm Soc Japan. 2012; 132 (12): 1365-1370.
16.Hathout RM, Mansour S, Mortada ND, Guinedi AS. Liposomes as an ocular delivery system for acetazolamide: in vitro and in vivo studies. AAPS PharmSciTech. 2007; 8(1) Article 1.
17.Zhang R, He R, Qian J, Guo J, Xue K, Yuan YF. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of tacrolimus encapsulated in liposomes. Invest Ophthal & Visual Sci. 2010; 51(7): 3575-82.
18.Mishra GP, Bagui M, Tamboli V, Mitra AK. Recent application of liposomes in ophthalmic drug delivery. J Drug Del. 2011; Article ID 863734. doi: 10.1155/2011/863734.
19.Sharif Makhmal Zadeh B, Aze Z, Azarpanah Z. Preparation and evaluation of mafenide acetate liposomal formulation as an eschar delivery system. Int J Drug Dev Res. 2011; 3(4): 129-140
20.Brandl M, Bachmann D, Drechsler M, Bauer K. Liposome preparation by a new high pressure homogenizer Gaulin Micron Lab 40. Drug Dev and Indust Pharm. 1990;16(14):2167-91.
21.Soga O, van Nostrum CF, Fens M, Rijcken C, Schiffelers RM, Storm G, Hennink WE. Thermoresponsive and biodegradable polymeric micelles for paclitaxel delivery. J Control Rel. 2005; 103 (2): 341-353.
22.Maekawa-Matsuura M, Fujeda K, Maekewa Y, Nishimura T, Nagase K, Kanazawa H. LAT1-Targeting thermoresponsive liposomes for effective cellular uptake by cancer cells. ACS Omega. 2019; 4: 6443-6451.
23.Zadeh BSM, Baratib N, Hassanib MH, Rahim F. Development of Solid lipid nanoparticles as Eschar delivery system for Nitrofurazone Using Taguchi Design Approach. Int J Res Pharm Sci. 2010; 1(4): 466-472.
24.Mady MM, Darwish MM, Khalil S, Khalil WM. Biophysical studies on chitosan-coated liposomes. Eur Biophy J. 2009;38(8):1127-1133.
24.Maestrelli F, Gonz lez-Rodr guez ML, Rabasco AM, Mura P. Effect of preparation technique on the properties of liposomes encapsulating ketoprofen? cyclodextrin complexes aimed for transdermal delivery. Int J Pharm. 2006;312(1-2):53-60.
25.Bhatia A, Kumar R, Katare OP. Tamoxifen in topical liposomes: development, characterization and in-vitro evaluation. J Pharm Pharm Sci. 2004;7(2):252-259.
26.Nie S, Hsiao WW, Pan W, Yang Z. Thermoresponsive pluronic F-127- based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell toxicity, and uptake studies. Int J Nanomed. 2011; 6: 151-166.
27.Oliveira Eloy J, deSouza MC, Petrilli R, Barcellos PA, Lee RJ, Marchetti JM. Liposomes as carriers for hydrophilic small molecule drugs. Strategies to enhance encapsulation and delivery. Colloids Surf B: Bio Interface. 2014; 123 (1): 345-363.
28. Arumugam K, Subramanian GS, Mallayasamy SR, Averineni RK, Reddy MS, Udupa, N. A study of rivastigmine liposomes for delivery into the brain through intranasal route. Acta Pham. 2008; 58: 287-297.
29. Mattheolabakis G, Nie T, Constantinides P, Rigas B. Sterically stabilized liposomes incorporating the novel anticancer agent phospho-ibuprofen (MDC-917): preparation, characterization, and in vitro in vivo evaluation. Pharm Res. 2012; 29(6): 1435-1443.
30. Sharif Makhmalzadeh B, Niro H, Rahim F, Esfahani G. Ocular delivery system for propranolol hydrochloride based on nanostructurred lipid carrier. Sci Pharm. 2018; 86: doi: 10.3390/scipharm86020016.
31.Ma C, Prabhu S. Characterization of a novel lyophilized chitosan hydrogel complex for the controlled release of a highly water-soluble drug, niacinamide. Int J Drug Del. 2011;3(1).