Advertisement

Drug Delivery and Translational Research

, Volume 9, Issue 6, pp 1067–1081 | Cite as

Recent advances in cyclosporine drug delivery: challenges and opportunities

  • Dhrumi Patel
  • Sarika WairkarEmail author
Review Article

Abstract

Cyclosporine has been established as a gold standard for its immunosuppressant action. Apart from this, the molecule is boon in treating broad spectrum of diseases like rheumatoid arthritis, psoriasis, and dry eye syndrome. The broad spectrum of cyclosporine demands efficient delivery systems by several routes. Neoral® and Sandimmune® are currently available formulations for oral route, whereas Restasis® is used for ocular delivery of cyclosporine. The available formulations serve the purpose only to a limited extent due to constraints like high molecular weight, low solubility, low permeability, bitter taste, and narrow therapeutic index of cyclosporine. Therefore, several novel formulations like microemulsion, self-emulsifying systems, nanoparticles, and microspheres were developed to overcome these constraints, exploring different routes like oral, ocular, and topical for cyclosporine. Additionally, iontophoresis and ultrasound-mediated delivery has also been studied to improve its poor permeability in topical delivery, whereas biodegradable implants were reported to increase the retention time in cornea and prolonged the release of cyclosporine by ocular route. Although these recent advances in cyclosporine delivery look promising, its clinical translation require in depth studies to deliver safe, efficacious, and stable formulation of cyclosporine. This review focuses on challenges of cyclosporine delivery and the recent advancements for overcoming the constraints.

Keywords

Cyclosporine Delivery constraints Advanced delivery Routes of administration 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kjer J, Debbab A, Aly AH, Proksch P. Methods for isolation of marine-derived endophytic fungi and their bioactive secondary products. Nat Protoc. 2010;5(3):479–90.  https://doi.org/10.1038/nprot.2009.233.CrossRefPubMedGoogle Scholar
  2. 2.
    Wu X, Stockdill JL, Wang P, Danishefsky SJ. Total synthesis of cyclosporine: access to N-methylated peptides via lsonitrile coupling reactions. J Am Chem Soc. 2010;132(12):4098–100.  https://doi.org/10.1021/ja100517v.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wenger RM. Synthesis of cyclosporine. Total syntheses of ‘cyclosporin A’ and ‘cyclosporin H’, two fungal metabolites isolated from the species Tolypocladium inflatum GAMS. Helv Chim Acta. 1984;67(2):502–25.  https://doi.org/10.1002/hlca.19840670220.
  4. 4.
    Bockus AT, Lexa KW, Pye CR, Kalgutkar AS, Gardner JW, Hund KCR, et al. Probing the physicochemical boundaries of cell permeability and oral bioavailability in lipophilic macrocycles inspired by natural products. J Med Chem. 2015;58(11):4581–9.  https://doi.org/10.1021/acs.jmedchem.5b00128.CrossRefGoogle Scholar
  5. 5.
    Chatterjee J, Gilon C, Hoffman A, Kessler H. N-methylation of peptides: a new perspective in medicinal chemistry. Acc Chem Res. 2008;41(10):1331–42.  https://doi.org/10.1021/ar8000603.CrossRefPubMedGoogle Scholar
  6. 6.
    Wenger RM. Synthesis of cyclosporine and analogues: structural requirements for immunosuppressive activity. Angew Chem Int Ed Engl. 1985;24(2):77–85.  https://doi.org/10.1002/anie.198500773.CrossRefGoogle Scholar
  7. 7.
    Eid R. Therapeutic review. J Exot Pet Med. 2018;27(1):46–51.  https://doi.org/10.1053/j.jepm.2017.10.016.CrossRefGoogle Scholar
  8. 8.
    Hernández GL, Volpert OV, Íñiguez MA, Lorenzo E, Martínez-Martínez S, Grau R, et al. Selective inhibition of vascular endothelial growth factor–mediated angiogenesis by cyclosporin a. J Exp Med. 2001;193(5):607–20.  https://doi.org/10.1084/jem.193.5.607.CrossRefGoogle Scholar
  9. 9.
    Wells GA, Haguenauer D, Shea B, Suarez-Almazor ME, Welch V, Tugwell P, et al. Cyclosporine for treating rheumatoid arthritis. Cochrane Database Syst Rev. 1998;(2).  https://doi.org/10.1002/14651858.CD001083.
  10. 10.
    Roekevisch E, Spuls PI, Kuester D, Limpens J, Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133(2):429–38.  https://doi.org/10.1016/j.jaci.2013.07.049.CrossRefPubMedGoogle Scholar
  11. 11.
    Garrod R. Pulmonary rehabilitation in older people. CJ Geriatr Med. 2006;8(1):18–21.  https://doi.org/10.3238/arztebl.2015.0071.CrossRefGoogle Scholar
  12. 12.
    Czogalla A. Oral cyclosporine A - the current picture of its liposomal and other delivery systems. Cell Mol Biol Lett. 2009;14(1):139–52.  https://doi.org/10.2478/s11658-008-0041-6.CrossRefPubMedGoogle Scholar
  13. 13.
    Guada M, Lasa-Saracíbar B, Lana H, Del Carmen Dios-Viéitez M, Blanco-Prieto MJ. Lipid nanoparticles enhance the absorption of cyclosporine A through the gastrointestinal barrier: in vitro and in vivo studies. Int J Pharm. 2016;500(1–2):154–61.  https://doi.org/10.1016/j.ijpharm.2016.01.037. CrossRefPubMedGoogle Scholar
  14. 14.
    Borel JF, Feurer C, Magnée C, Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977;32(6):1017–25.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Gauchat J, Khandjian EW, Weil R. Cyclosporin A prevents induction of the interleukin 2 receptor gene in cultured murine thymocytes. Proc Natl Acad Sci U S A. 1986;83(September):6430–4.CrossRefGoogle Scholar
  16. 16.
    Colombani PM, Robb A, Hess AD. Cyclosporin a binding to calmodulin: a possible site of action on T lymphocytes. Science. 1985;228(4697):337–9.  https://doi.org/10.1126/science.3885394.CrossRefGoogle Scholar
  17. 17.
    Matsuda S, Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology. 2000;47(2–3):119–25.  https://doi.org/10.1016/S0162-3109(00)00192-2.CrossRefPubMedGoogle Scholar
  18. 18.
    Krönke M, Leonard WJ, Depper JM, Arya SK, Wong-Staal F, Gallo RC, et al. Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984;81(16):5214–8.  https://doi.org/10.1073/pnas.81.16.5214.CrossRefGoogle Scholar
  19. 19.
    Schmid FX. Protein folding: prolyl isomerases join the fold. Curr Biol. 1995;5(9):993–4.  https://doi.org/10.1016/S0960-9822(95)00197-7.CrossRefPubMedGoogle Scholar
  20. 20.
    Sigal NH. Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A? J Exp Med. 1991;173(3):619–28.  https://doi.org/10.1084/jem.173.3.619.CrossRefGoogle Scholar
  21. 21.
    Kiefer F, Tibbles LA, Anafi M, Janssen A, Zanke BW, Lassam N, et al. HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. EMBO J. 1996;15(24):7013–25.CrossRefGoogle Scholar
  22. 22.
    Klahr S, Ishidoya S, Morrissey J. Role of angiotensin II in the tubulointerstitial fibrosis of obstructive nephropathy. Am J Kidney Dis. 1995;26(1):141–6.CrossRefGoogle Scholar
  23. 23.
    Matsuda S, Moriguchi T, Koyasu S, Nishida E. T lymphocyte activation signals for interleukin-2 production involve activation of MKK6-p38 and MKK7-SAPK/JNK signaling pathways sensitive to cyclosporin A. J Biol Chem. 1998;273(20):12378–82.  https://doi.org/10.1074/jbc.273.20.12378.CrossRefPubMedGoogle Scholar
  24. 24.
    Granelli-Piperno A. In situ hybridization for interleukin 2 and interleukin 2 receptor mRNA in T cells activated in the presence or absence of cyclosporin A. J Exp Med. 1988;168(5):1649–58.  https://doi.org/10.1084/jem.168.5.1649.CrossRefPubMedGoogle Scholar
  25. 25.
    Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9(2):180–6.  https://doi.org/10.1016/S0955-0674(97)80061-0.CrossRefPubMedGoogle Scholar
  26. 26.
    Miskin JE, Charles CA, Lynnette CG, Dixon LA. Viral mechanism for inhibition of the cellular phosphatase calcineurin. Science. 1998;281(July):562–5.CrossRefGoogle Scholar
  27. 27.
    Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93(2):215–28.  https://doi.org/10.1016/S0092-8674(00)81573-1.CrossRefGoogle Scholar
  28. 28.
    Timmerman LA, Clipstone NA, Ho SN, Northrop JP, Crabtree GR. Rapid shuttling of NF-AT in discrimination of Ca2+signals and immunosuppression. Nature. 1996;383:837–40.  https://doi.org/10.1038/383837a0.CrossRefPubMedGoogle Scholar
  29. 29.
    Su B, Jacinto E, Hibi M, Kallunki T, Karin M, Ben-Neriah Y. JNK is involved in signal integration during costimulation of T lymphocytes. Cell. 1994;77(5):727–36.  https://doi.org/10.1016/0092-8674(94)90056-6.CrossRefPubMedGoogle Scholar
  30. 30.
    Su B, Karint M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol. 1996;8(3):402–11.  https://doi.org/10.1016/S0952-7915(96)80131-2.CrossRefPubMedGoogle Scholar
  31. 31.
    Yang SG. Biowaiver extension potential and IVIVC for BCS class II drugs by formulation design: case study for cyclosporine self-microemulsifying formulation. Arch Pharm Res. 2010;33(11):1835–42.  https://doi.org/10.1007/s12272-010-1116-2.CrossRefPubMedGoogle Scholar
  32. 32.
    Charman WN, Porter CJH, Mithani S, Dressman JB. Physicochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. J Pharm Sci. 1997;86(3):269–82.  https://doi.org/10.1021/js960085v.CrossRefPubMedGoogle Scholar
  33. 33.
    Fahr A. Cyclosporin clinical pharmacokinetics. Clin Pharmacokinet. 1993;24(6):472–95.  https://doi.org/10.2165/00003088-199324060-00004.CrossRefPubMedGoogle Scholar
  34. 34.
    Higgins C, Barnard A, Nixon R. Nanotechnology and contact dermatitis: applications and implications. Contact Dermatitis. 2016;75(3):77–8.Google Scholar
  35. 35.
    Müller RH, Runge S, Ravelli V, Mehnert W, Thünemann AF, Souto EB. Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN®) versus drug nanocrystals. Int J Pharm. 2006;317(1):82–9.  https://doi.org/10.1016/j.ijpharm.2006.02.045.CrossRefPubMedGoogle Scholar
  36. 36.
    Powles AV, Hardman CM, Porter WM, Cook T, Hulme B, Fry L. Renal function after 10 years treatment with cyclosporin for psoriasis. Br J Dermatol. 1998;138(3):443–9.  https://doi.org/10.1046/j.1365-2133.1998.02122.x.CrossRefPubMedGoogle Scholar
  37. 37.
    Thaçi D, Bräutigam M, Kaufmann R, Weidinger G, Paul C, Christophers E. Body-weight-independent dosing of cyclosporine micro-emulsion and three times weekly maintenance regimen in severe psoriasis. A randomised study. Dermatology. 2002;205(4):383–8.  https://doi.org/10.1159/000066425.CrossRefPubMedGoogle Scholar
  38. 38.
    Czech W, Bräutigam M, Weidinger G, Schöpf E. A body-weight-independent dosing regimen of cyclosporine microemulsion is effective in severe atopic dermatitis and improves the quality of life. J Am Acad Dermatol. 2000;42(4):653–9.  https://doi.org/10.1016/S0190-9622(00)90180-4.CrossRefPubMedGoogle Scholar
  39. 39.
    Oates JA, Wood AJJ, Kahan BD. Cyclosporine. N Engl J Med. 1989;321(25):1725–38.  https://doi.org/10.1056/NEJM198912213212507.CrossRefGoogle Scholar
  40. 40.
    Copeland KR, Yatscoff RW, McKenna R. Immunosuppressive activity of cyclosporine metabolites compared and characterized by mass spectroscopy and nuclear magnetic resonance. Clin Chem. 1990;36(2):225–9.PubMedGoogle Scholar
  41. 41.
    Pickrell MD, Sawers R, Michael J. Pregnancy after renal transplantation: severe intrauterine growth retardation during treatment with cyclosporin A. Br Med J (Clin Res Ed). 1988;296(6625):825–6.  https://doi.org/10.1136/bmj.296.6625.825-a.CrossRefGoogle Scholar
  42. 42.
    Rajfer J, Sikka SC, Lemmi C, Koyle MA. Cyclosporine inhibits testosterone biosynthesis in the rat testis. Endocrinology. 1987;121(2):586–9.  https://doi.org/10.1210/endo-121-2-586.CrossRefPubMedGoogle Scholar
  43. 43.
    Robson D. Review of the pharmacokinetics, interactions and adverse reactions of cyclosporine in people, dogs and cats. Vet Rec. 2003;152(24):739–48.  https://doi.org/10.1136/vr.152.24.739.CrossRefGoogle Scholar
  44. 44.
    Vercauteren SB, Bosmans JL, Elseviers MM, Verpooten GA, De Broe ME. A meta-analysis and morphological review of cyclosporine-induced nephrotoxicity in auto-immune diseases. Kidney Int. 1998;54(2):536–45.  https://doi.org/10.1046/j.1523-1755.1998.00017.x.CrossRefPubMedGoogle Scholar
  45. 45.
    Mohammadpour N, Elyasi S, Vahdati N, Mohammadpour AH, Shamsara J. A review on therapeutic drug monitoring of immunosuppressant drugs. Iran J Basic Med Sci. 2011;14(6):485–98.  https://doi.org/10.1046/j.1365-2125.1999.00911.x.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Aguirre TAS, Teijeiro-Osorio D, Rosa M, Coulter IS, Alonso MJ, Brayden DJ. Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials. Adv Drug Deliv Rev. 2016;106:223–41.  https://doi.org/10.1016/j.addr.2016.02.004.CrossRefPubMedGoogle Scholar
  47. 47.
    Reichrath J, Bens G, Bonowitz A, Tilgen W. Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients. J Am Acad Dermatol. 2005;53(2):273–83.  https://doi.org/10.1016/j.jaad.2004.10.006.CrossRefPubMedGoogle Scholar
  48. 48.
    Wilson SE, Perry HD. Long-term resolution of chronic dry eye symptoms and signs after topical cyclosporine treatment. Ophthalmology. 2007;114(1):76–9.  https://doi.org/10.1016/j.ophtha.2006.05.077.CrossRefGoogle Scholar
  49. 49.
    Hernández-García V. Contents of the digestive tract of a false killer whale (Pseudorca crassidens) stranded in Gran Canaria (Canary Islands, Central East Atlantic). Bull Mar Sci. 2002;71(1):367–9.  https://doi.org/10.1002/bdd.CrossRefGoogle Scholar
  50. 50.
    Tao XR, Xia XY, Zhang J, Tong LY, Zhang W, Zhou X, et al. CYP3A4∗18B and CYP3A5∗3 polymorphisms contribute to pharmacokinetic variability of cyclosporine among healthy Chinese subjects. Eur J Pharm Sci. 2015;76:238–44.  https://doi.org/10.1016/j.ejps.2015.05.011.CrossRefGoogle Scholar
  51. 51.
    Muheem A, Shakeel F, Jahangir MA, Anwar M, Mallick N, Jain GK, et al. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm J. 2016;24(4):413–28.  https://doi.org/10.1016/j.jsps.2014.06.004.CrossRefGoogle Scholar
  52. 52.
    Vasconcelos T, Marques S, Sarmento B. Measuring the emulsification dynamics and stability of self-emulsifying drug delivery systems. Eur J Pharm Biopharm. 2018;123:1–8.  https://doi.org/10.1016/j.ejpb.2017.11.003.CrossRefPubMedGoogle Scholar
  53. 53.
    Yu JY, Chong PHJ. A survey of clustering schemes for mobile ad hoc networks. IEEE Commun Surv Tutorials. 2005;7(1):32–47.  https://doi.org/10.1080/17425247.2016.1218462.CrossRefGoogle Scholar
  54. 54.
    Zhang X, Yi Y, Qi J, Lu Y, Tian Z, Xie Y, et al. Controlled release of cyclosporine A self-nanoemulsifying systems from osmotic pump tablets: near zero-order release and pharmacokinetics in dogs. Int J Pharm. 2013;452(1–2):233–40.  https://doi.org/10.1016/j.ijpharm.2013.05.014.CrossRefGoogle Scholar
  55. 55.
    Zhao X, Zhou YQ, Potharaju S, Lou H, Sun HM, Brunson E, et al. Development of a self micro-emulsifying tablet of cyclosporine A by the liquisolid compact technique. Int J Pharm Sci Res. 2011;2(9):2299–308.Google Scholar
  56. 56.
    Zidan AS, Aljaeid BM, Mokhtar M, Shehata TM. Taste-masked orodispersible tablets of cyclosporine self-nanoemulsion lyophilized with dry silica. Pharm Dev Technol. 2015;20(6):652–61.  https://doi.org/10.3109/10837450.2014.908307.CrossRefPubMedGoogle Scholar
  57. 57.
    Mukund JY, Kantilal BR, Sudhakar RN. Floating microspheres: a review. Braz J Pharm Sci. 2012;48(1):17–30.  https://doi.org/10.1590/S1984-82502012000100003.CrossRefGoogle Scholar
  58. 58.
    Lee J, Park TG, Choi H. Development of oral drug delivery system using floating microspheres. J Microencapsul. 1999;16:715–29.  https://doi.org/10.1080/026520499288663.
  59. 59.
    Kaurav H, Hari Kumar SL, Kaur A. Mucoadhesive microspheres as carriers in drug delivery: a review. Int J Drug Dev Res. 2012;4(2):21–34.  https://doi.org/10.1002/rnc.CrossRefGoogle Scholar
  60. 60.
    Malaekeh-Nikouei B, Sajadi Tabassi SA, Jaafari MR. Preparation, characterization, and mucoadhesive properties of chitosan-coated microspheres encapsulated with cyclosporine A. Drug Dev Ind Pharm. 2008;34(5):492–8.  https://doi.org/10.1080/03639040701744004.CrossRefPubMedGoogle Scholar
  61. 61.
    Labbé A, Baudouin C, Ismail D, Amrane M, Garrigue JS, Leonardi A, et al. Utilisation de la cyclosporine A topique : une étude pan-européenne. J Fr Ophtalmol. 2017;40(3):187–95.  https://doi.org/10.1016/j.jfo.2016.12.004.CrossRefGoogle Scholar
  62. 62.
    Agarwal P, Rupenthal ID. Modern approaches to the ocular delivery of cyclosporine A. Drug Discov Today. 2016;21(6):977–88.  https://doi.org/10.1016/j.drudis.2016.04.002.CrossRefPubMedGoogle Scholar
  63. 63.
    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.  https://doi.org/10.1016/j.ejpb.2017.03.006.CrossRefPubMedGoogle Scholar
  64. 64.
    Dahan A, Zimmermann EM, Ben-Shabat S. Modern prodrug design for targeted oral drug delivery. Molecules. 2014;19(10):16489–505.  https://doi.org/10.3390/molecules191016489.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Hamel AR, Hubler F, Mutter M. Water-soluble prodrugs of cyclosporine A with tailored conversion rates. J Pept Res. 2005;65(3):364–74.  https://doi.org/10.1111/j.1399-3011.2005.00234.x.CrossRefPubMedGoogle Scholar
  66. 66.
    Rodriguez-Aller M, Guillarme D, El Sanharawi M, Behar-Cohen F, Veuthey JL, Gurny R. In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application. J Control Release. 2013;170(1):153–9.  https://doi.org/10.1016/j.jconrel.2013.04.019.CrossRefPubMedGoogle Scholar
  67. 67.
    Battaglia L, Gallarate M, Serpe L, Foglietta F, Muntoni E, del Pozo Rodriguez A, et al. Chapter 7. In: Ocular delivery of solid lipid nanoparticles: Elsevier Inc; 2018.  https://doi.org/10.1016/B978-0-12-813687-4.00007-4.CrossRefGoogle Scholar
  68. 68.
    Gökçe EH, Sandri G, Eǧrilmez S, Bonferoni MC, Güneri T, Caramella C. Cyclosporine a-loaded solid lipid nanoparticles: ocular tolerance and in vivo drug release in rabbit eyes. Curr Eye Res. 2009;34(11):996–1003.  https://doi.org/10.3109/02713680903261405.CrossRefGoogle Scholar
  69. 69.
    Lallemand F, Felt-Baeyens O, Besseghir K, Behar-Cohen F, Gurny R. Cyclosporine A delivery to the eye: a pharmaceutical challenge. Eur J Pharm Biopharm. 2003;56(3):307–18.  https://doi.org/10.1016/S0939-6411(03)00138-3.CrossRefPubMedGoogle Scholar
  70. 70.
    Başaran E, Demirel M, Sirmagül B, Yazan Y. Cyclosporine-A incorporated cationic solid lipid nanoparticles for ocular delivery. J Microencapsul. 2010;27(1):37–47.  https://doi.org/10.3109/02652040902846883.CrossRefPubMedGoogle Scholar
  71. 71.
    Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev Drug Discov. 2014;13(9):655–72.  https://doi.org/10.1038/nrd4363.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Alghadyan AA, Peyman GA, Khoobehi B, Milner S, Liu K. Liposome-bound cyclosporine : clearance after intravitreal injection. Int Ophthalmol. 1988;12(2):109–12.  https://doi.org/10.1007/BF0013713.CrossRefPubMedGoogle Scholar
  73. 73.
    He Y, Wang J-C, Liu Y-L, Ma Z-Z, Zhu X-A, Zhang Q. Therapeutic and toxicological evaluations of cyclosporine a microspheres as a treatment vehicle for uveitis in rabbits. J Ocul Pharmacol Ther. 2006;22(2):121–31.  https://doi.org/10.1089/jop.2006.22.121.CrossRefGoogle Scholar
  74. 74.
    Cao Y, Zhang C, Shen W, Cheng Z, Yu L, Ping Q. Poly(N-isopropylacrylamide)-chitosan as thermosensitive in situ gel-forming system for ocular drug delivery. J Control Release. 2007;120(3):186–94.  https://doi.org/10.1016/j.jconrel.2007.05.009. CrossRefGoogle Scholar
  75. 75.
    Wu Y, Yao J, Zhou J, Dahmani FZ. Enhanced and sustained topical ocular delivery of cyclosporine a in thermosensitive hyaluronic acid-based in situ forming microgels. Int J Nanomedicine. 2013;8:3587–601.  https://doi.org/10.2147/IJN.S47665.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Kapoor Y, Chauhan A. Ophthalmic delivery of Cyclosporine A from Brij-97 microemulsion and surfactant-laden p-HEMA hydrogels. Int J Pharm. 2008;361(1–2):222–9.  https://doi.org/10.1016/j.ijpharm.2008.05.028.CrossRefPubMedGoogle Scholar
  77. 77.
    Lee D. Intraocular implants for the treatment of autoimmune uveitis. J Funct Biomater. 2015;6(3):650–66.  https://doi.org/10.3390/jfb6030650.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Apel A, Oh C, Chiu R, Saville B, Cheng YL, Rootman D. A subconjunctival degradable implant for cyclosporine delivery in corneal transplant therapy. Curr Eye Res. 1995;14(8):659–67.  https://doi.org/10.3109/02713689508998493.CrossRefPubMedGoogle Scholar
  79. 79.
    Musa SH, Basri M, Masoumi HRF, Shamsudin N, Salim N. Enhancement of physicochemical properties of nanocolloidal carrier loaded with cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo hydrating action. Int J Nanomedicine. 2017;12:2427–41.  https://doi.org/10.2147/IJN.S125302.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Katare O, Raza K, Singh B, Dogra S. Novel drug delivery systems in topical treatment of psoriasis: rigors and vigors. Indian J Dermatol Venereol Leprol. 2010;76(6):612.  https://doi.org/10.4103/0378-6323.72451.CrossRefPubMedGoogle Scholar
  81. 81.
    Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2012;64(SUPPL):175–93.  https://doi.org/10.1016/j.addr.2012.09.018.CrossRefGoogle Scholar
  82. 82.
    Liu H, Li S, Wang Y, Han F, Dong Y. Bicontinuous water-AOT/Tween85-isopropyl myristate microemulsion: a new vehicle for transdermal delivery of cyclosporin A. Drug Dev Ind Pharm. 2006;32(5):549–57.  https://doi.org/10.1080/03639040500529168.CrossRefPubMedGoogle Scholar
  83. 83.
    Marwah H, Garg T, Goyal AK, Rath G. Permeation enhancer strategies in transdermal drug delivery. Drug Deliv. 2016;23(2):564–78.  https://doi.org/10.3109/10717544.2014.935532.CrossRefPubMedGoogle Scholar
  84. 84.
    Lopes LB, Collett JH, Bentley MVLB. Topical delivery of cyclosporin A: an in vitro study using monoolein as a penetration enhancer. Eur J Pharm Biopharm. 2005;60(1):25–30.  https://doi.org/10.1016/j.ejpb.2004.12.003.CrossRefPubMedGoogle Scholar
  85. 85.
    Lauterbach A, Müller-Goymann CC. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route. Eur J Pharm Biopharm. 2015;97(July):152–63.  https://doi.org/10.1016/j.ejpb.2015.06.020.CrossRefPubMedGoogle Scholar
  86. 86.
    Sawant K, Varia J, Dodiya S. Cyclosporine a loaded solid lipid nanoparticles: optimization of formulation, process variable and characterization. Curr Drug Deliv. 2008;5(1):64–9.  https://doi.org/10.2174/156720108783331069.CrossRefPubMedGoogle Scholar
  87. 87.
    Kim ST, Jang DJ, Kim JH, Park JY, Lim JS, Lee SY, et al. Topical administration of cyclosporin A in a solid lipid nanoparticle formulation. Pharmazie. 2009;64(8):510–4.  https://doi.org/10.1691/ph.2009.8373.
  88. 88.
    Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. Arab J Chem. 2017.  https://doi.org/10.1016/j.arabjc.2017.05.011.CrossRefGoogle Scholar
  89. 89.
    Kotsuchibashi Y, Nakagawa Y, Ebara M. Nanoparticles. Biomater Nanoarchitectonics. 2016;5(June):7–23.  https://doi.org/10.1016/B978-0-323-37127-8.00002-9.CrossRefGoogle Scholar
  90. 90.
    Frušić-Zlotkin M, Soroka Y, Tivony R, Larush L, Verkhovsky L, Brégégère FM, et al. Penetration and biological effects of topically applied cyclosporin A nanoparticles in a human skin organ culture inflammatory model. Exp Dermatol. 2012;21(12):938–43.  https://doi.org/10.1111/exd.12051.CrossRefGoogle Scholar
  91. 91.
    Alkilani AZ, McCrudden MTC, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438–70.  https://doi.org/10.3390/pharmaceutics7040438.CrossRefGoogle Scholar
  92. 92.
    Boinpally RR, Zhou SL, Devraj G, Anne PK, Poondru S, Jasti BR. Iontophoresis of lecithin vesicles of cyclosporin A. Int J Pharm. 2004;274(1–2):185–90.  https://doi.org/10.1016/j.ijpharm.2004.01.016.CrossRefGoogle Scholar
  93. 93.
    Guo J, Ping Q, Sun G, Jiao C. Lecithin vesicular carriers for transdermal delivery of cyclosporin A. Int J Pharm. 2000;194(2):201–7.  https://doi.org/10.1016/S0378-5173(99)00361-0.CrossRefPubMedGoogle Scholar
  94. 94.
    Park D, Park H, Seo J, Lee S. Sonophoresis in transdermal drug deliverys. Ultrasonics. 2014;54(1):56–65.  https://doi.org/10.1016/j.ultras.2013.07.007.CrossRefPubMedGoogle Scholar
  95. 95.
    Liu H, Li S, Pan W, Wang Y, Han F, Yao H. Investigation into the potential of low-frequency ultrasound facilitated topical delivery of cyclosporin A. Int J Pharm. 2006;326(1–2):32–8.  https://doi.org/10.1016/j.ijpharm.2006.07.022.CrossRefPubMedGoogle Scholar
  96. 96.
    Koppelstaetter C, Kern G, Leierer G, Mair SM, Mayer G, Leierer J. Effect of cyclosporine, tacrolimus and sirolimus on cellular senescence in renal epithelial cells. Toxicol in Vitro. 2018;48(September 2017):86–92.  https://doi.org/10.1016/j.tiv.2018.01.004.CrossRefPubMedGoogle Scholar
  97. 97.
    Kvien TK, Scherer HU, Burmester GR. Rheumatoid Arthritis. EULAR Compend Rheum Dis. 2009;333(3):61–80.  https://doi.org/10.1038/nrrheum.2009.31.CrossRefGoogle Scholar
  98. 98.
    Stevenson D, Tauber J, Reis BL. Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-servere dry eye disease: a dose-ranging, randomized trial. Ophthalmology. 2000;107(5):967–74.  https://doi.org/10.1016/S0161-6420(00)00035-X.CrossRefPubMedGoogle Scholar
  99. 99.
    Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclosporine: pharmacology and clinical uses. Surv Ophthalmol. 2009;54(3):321–38.  https://doi.org/10.1016/j.survophthal.2009.02.002.CrossRefGoogle Scholar
  100. 100.
    Biren TA, Barr RJ. Dermatologic applications of cyclosporine. Arch Dermatol. 1986;122(9):1028–32.  https://doi.org/10.1001/archderm.1986.01660210078022.CrossRefPubMedGoogle Scholar
  101. 101.
    Lebwohl M, Ellis C, Gottlieb A, Koo J, Krueger G, Linden K, et al. Cyclosporine consensus conference: with emphasis on the treatment of psoriasis. J Am Acad Dermatol. 1998;39(3):464–75.  https://doi.org/10.1016/S0190-9622(98)70325-1.CrossRefGoogle Scholar
  102. 102.
    Dorinda Shelley E, Shelley WB. Cyclosporine therapy for pyoderma gangrenosum associated with sclerosing cholangitis and ulcerative colitis. J Am Acad Dermatol. 1988;18:1084–8.  https://doi.org/10.1016/S0190-9622(88)70111-5.CrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Shobhaben Pratapbhai Patel School of Pharmacy & Technology ManagementSVKM’s NMIMSMumbaiIndia

Personalised recommendations