Enhanced Corneal Permeation of Pilocarpine Using Liposome Technology

Document Type : Original Article

Authors

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

2 Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Background: A novel liposomal pilocarpine formulation as an ophthalmic drug delivery system has been designed to treat patients with glaucoma. The purpose of the present study was to formulate and evaluate liposomes loaded with pilocarpine and to evaluate permeation through rabbit cornea.
Method: Liposomes containing pilocarpine were prepared using thin film method. The quantities of soya lecithin and cholesterol were changed to enhance the encapsulation of the drug. The physicochemical properties of the prepared liposomes were evaluated according to their viscosity, pH, particle size, in vitro drug release, and transcorneal rabbit permeation. Dialysis membrane method was utilized to assess drug release profile.
Results: The results indicated that the mean particle sizes of liposomes were 120.5-212 nm and the pH and viscosity of formulations were in the range of 6.30-6.63 and 43.85-80.1 cps, respectively. According to the release study results, maximumally 60% of the drug released from liposomal formulations after 24 hours of the experiment. Also, the cumulative percentage of the drug permeated through rabbit cornea was differing from 3.86 to 14.9%. Irrespective from the composition and characteristics of the different liposomal formulations, they significantly increased the drug partitioning, permeability coefficient and flux of pilocarpine in rabbit cornea ex vivo model in comparison to control drug solution.
Conclusion: The present study proved that any alteration in composition and nature of pilocarpine liposomal formulations may affect the drug permeability parameters through corneal membrane and also physico-chemical properties. It is probably due to the change in corneal structure in the presence of different liposomes composition.

Keywords


  1. Tsai CH, Wang PY, Lin IC, Huang H, Liu GS, Tseng CL. Ocular drug delivery: role of degradable polymeric nanocarriers for ophthalmic application. Int J Mol Sci 2018; 19(9):2830. doi: 10.3390/ijms19092830.
  2. Choi SW, Kim J. Therapeutic contact lenses with polymeric vehicles for ocular drug delivery: a review. Materials (Basel) 2018; 11(7):1125. doi: 10.3390/ma11071125.
  3. Moghimipour E, Salimi A, Monjezi M. Formulation and evaluation of liposomes for transdermal delivery of celecoxib. Jundishapur J Nat Pharm Prod 2015; 10(1):e17653. doi: 10.17795/jjnpp-17653.
  4. Skaat A, Rosman MS, Chien JL, Mogil RS, Ren R, Liebmann JM, et al. Effect of pilocarpine hydrochloride on the schlemm canal in healthy eyes and eyes with open-angle glaucoma. JAMA Ophthalmol 2016; 134(9):976-81. doi: 10.1001/jamaophthalmol.2016.1881.
  5. Flocks M, Zweng HC. Studies on the mode of action of pilocarpine on aqueous outflow. Am J Ophthalmol 1957; 44(5 Pt 2):380-6. doi: 10.1016/0002-9394(57)93136-7.
  6. Neufeld AH. Experimental studies on the mechanism of action of timolol. Survey of Ophthalmology 1979; 23(6):363-70. doi: 10.1016/0039-6257(79)90229-7.
  7. Lopes LB, Scarpa MV, Pereira NL, Oliveira LC, Oliveira AG. Interaction of sodium diclofenac with freeze-dried soya phosphatidylcholine and unilamellar liposomes. Revista Brasileira de Ciências Farmacêuticas 2006; 42(4):497-504. doi: 10.1590/S1516-93322006000400004.
  8. Moghimipour E, Rezaei M, Kouchak M, Ramezani Z, Amini M, Ahmadi Angali K, et al. A mechanistic study of the effect of transferrinconjugation on cytotoxicity of targeted liposomes. J Microencapsul 2018; 35(6):548-58. doi: 10.1080/02652048.2018.
  9. Daraee H, Etemadi A, Kouhi M, Alimirzalu S, Akbarzadeh A. Application of liposomes in medicine and drug delivery. Artif Cells Nanomed Biotechnol 2016; 44(1):381-91. doi: 10.3109/21691401.2014.953633.
  10. Bunker A, Magarkar A, Viitala T. Rational design of liposomal drug delivery systems, a review: combined experimental and computational studies of lipid membranes, liposomes and their PEGylation. Biochim Biophys Acta 2016; 1858(10):2334-52. doi: 10.1016/j.bbamem.2016.02.025.
  11. Ali MH, Moghaddam B, Kirby DJ, Mohammed AR, Perrie Y. The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs. Int J Pharm 2013; 453(1):225-32. doi: 10.1016/j.ijpharm.2012.06.056.
  12. Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, Angali KA, et al. Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil. Eur J Pharm Sci 2018; 114:166-174. doi: 10.1016/j.ejps.2017.12.011.
  13. Eloy JO, Claro de Souza M, Petrilli R, Barcellos JP, Lee RJ, Marchetti JM. Liposomes as carriers of hydrophilic small molecule drugs: strategies to enhance encapsulation and delivery. Colloids Surf B Biointerfaces 2014; 123:345-63. doi: 10.1016/j.colsurfb.2014.09.029.
  14. Mohammadi-Samani S, Montaseri H, Jamshidnejad M. Preparation and evaluation of cyproterone acetate liposome for topical drug delivery. Iranian Journal of Pharmaceutical Sciences 2009; 5(4):199-204.
  15. Benson H. Permeability of the cornea to topically applied drugs. Arch Ophthalmol 1974; 91(4):313-27. doi: 10.1001/archopht.1974.03900060323017.
  16. Bloomfield SE, Miyata T, Dunn MW, Bueser N, Stenzel KH, Rubin AL. Soluble gentamicin ophthalmic inserts as a drug delivery system. Arch Ophthalmol 1978; 96(5):885-7. doi: 10.1001/archopht.1978.03910050487020.
  17. Hanna C. Delivery of antibiotics to the eye. Life Sci 1980; 27(25-26):2509-12. doi: 10.1016/0024-3205(80)90530-5.
  18. Hanna C, Massey JY, Hendrickson RO, Williamson J, Jones EM, Wilson P. Ocular penetration of topical chloramphenicol in humans. Arch Ophthalmol 1978; 96(7):1258-61. doi: 10.1001/archopht.1978.03910060084018.
  19. Patton TF, Francoeur M. Ocular bioavailability and systemic loss of topically applied ophthalmic drugs. Am J Ophthalmol 1978; 85(2):225-9. doi: 10.1016/s0002-9394(14)75953-7.
  20. Salminen L, Urtti A, Periviita L. Effect of ocular pigmentation on pilocarpine pharmacology in the rabbit eye. I. Drag distribution and metabolism. Int J Pharm 1984; 18(1-2):17-24. doi: 10.1016/0378-5173(84)90103-0.
  21. Niesman MR. The use of liposomes as drug carriers in ophthalmology. Crit Rev Ther Drug Carrier Syst 1992; 9(1):1-38.
  22. Salimi A, Gobadian H, Sharif Makhmalzadeh B. Dermal pharmacokinetics of rivastigmine-loaded liposomes: an ex vivo-in vivo correlation study. J Liposome Res 2021; 31(3):246-54. doi: 10.1080/08982104.2020.1787440.
  23. Meisner D, Mezei M. Liposome ocular delivery systems. Adv Drug Deliv Rev 1995; 16(1):75-93. doi: 10.1016/0169-409X(95)00016-Z.
  24. O'Donnell JJ, Sandman R, Drake MV. Measurement of pilocarpine and its degradation products by high-performance liquid chromatography. J Pharm Sci 1980; 69(9):1096-7. doi: 10.1002/jps.2600690930.
  25. Dua JS, Rana PA, Bhandari AK. Liposome: methods of preparation and applications. Int J Pharm Stud Res 2012; 3(2):14-20.
  26. Moghimipour E, Salimi A, Eftekhari S. Design and characterization of microemulsion systems for naproxen. Adv Pharm Bull 2013; 3(1): 63-71. doi: 10.5681/apb.2013.011.
  27. Amado JR, Prada AL, Duarte JL, Keita H, da Silva HR, Ferreira AM, et al. Development, stability and in vitro delivery profile of new loratadine-loaded nanoparticles. Saudi Pharm J 2017; 25(8):1158-68. doi: 10.1016/j.jsps.2017.07.008.
  28. Salimi A, Sharif Makhmalzadeh B, Moghimipour E. Preparation and characterization of cyanocobalamin (vit B12) microemulsion properties and structure for topical and transdermal application. Iran J Basic Med Sci 2013; 16(7):865-72.
  29. Budai L, Hajdú M, Budai M, Gróf P, Béni S, Noszál B, et al. Gels and liposomes in optimized ocular drug delivery: studies on ciprofloxacin formulations. Int J Pharm 2007; 343(1-2):34-40. doi: 10.1016/j.ijpharm.2007.04.013.
  30. Mergler S, Pleyer U. The human corneal endothelium: new insights into electrophysiology and ion channels. Prog Retin Eye Res 2007; 26(4):359-78. doi: 10.1016/j.preteyeres.2007.02.001.
  31. Greenbaum A, Hasany SM, Rootman D. Optisol vs Dexsol as storage media for preservation of human corneal epithelium. Eye (Lond) 2004; 18(5):519-24. doi: 10.1038/sj.eye.6700693.
  32. Dai Y, Zhou R, Liu L, Lu Y, Qi J, Wu W. Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation. Int J Nanomedicine 2013; 8:1921-33. doi: 10.2147/IJN.S44487.
  33. 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):1. doi: 10.1208/pt0801001.
  34. Nagarsenker MS, Londhe VY. Preparation and evaluation of a liposomal formulation of sodium cromoglicate. Int J Pharm 2003; 251(1-2):49-56. doi: 10.1016/s0378-5173(02)00583-5.
  35. Li J, Wu L, Wu W, Wang B, Wang Z, Xin H, et al. A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate. Int J Pharm. 2013; 455(1-2):75-84. doi: 10.1016/j.ijpharm.2013.07.057.
  36. Wang X, Zhang Y, Huang J, Xia M, Liu L, Tian C, et al. Self-assembled hexagonal liquid crystalline gels as novel ocular formulation with enhanced topical delivery of pilocarpine nitrate. Int J Pharm 2019; 562:31-41. doi: 10.1016/j.ijpharm.2019.02.033.
  37. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems--recent advances. Prog Retin Eye Res 1998; 17(1):33-58. doi: 10.1016/s1350-9462(97)00002-5.
  38. Xu J, Xue Y, Hu G, Lin T, Gou J, Yin T, et al. A comprehensive review on contact lens for ophthalmic drug delivery. J Control Release 2018; 281:97-118. doi: 10.1016/j.jconrel.2018.05.020.