[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

Ultraflexible lipid vesicles allow topical absorption of cyclosporin A

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Psoriasis and atopic dermatitis are widespread pathologies with a need to improve their treatment. Topical administration of cyclosporine A (CyA) could be used if targeted to the skin, thus avoiding systemic levels. Unfortunately, CyA molecular weight and lipophilicity prevent its diffusion through human skin. Four novel lipid vesicles have been prepared by different methodologies to overcome this problem. The vesicles were characterized in terms of particle size, size polydispersity, Z-potential, morphology, drug encapsulation, phospholipid content, and vesicle flexibility. Freeze-drying in presence and absence of cryoprotective agents was also performed, to guarantee long-term stability. The ability to deliver CyA into the skin was assessed using human epidermis in Franz diffusion cells and compared with the delivery of drug solutions with enhancers. The technical characteristics of four types of vesicle make them suitable to carry drugs. Moreover, these liposomal formulations were able to effectively deliver CyA in vitro into the skin. The present work introduces a promising approach for the topical treatment of skin pathologies with an immune component.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CyA:

Cyclosporine A

CL:

Conventional liposomes

CL-SON:

Sonicated conventional liposomes

CL-EXT:

Extruded conventional liposomes

Cv:

Concentration of drug in the donor compartment

DLS:

Dynamic light scattering

EE%:

Encapsulation efficiency

Etho:

Ethosomes

Etho-EXT:

Extruded ethosomes

HHSE:

Human heat-separated epidermis

J :

Flux

J max :

Maximum flux

J SS :

Steady-state flux

MLV:

Multilamellar vesicles

PBS:

Phosphate buffer solution

PC:

Phosphatidylcholine

PC%:

Phosphatidylcholine content

PDI:

Polydispersity index

Q :

Amount

S v :

Solubility of the drug in the vehicle

TEM:

Transmission electron microscopy

T1:

Transfersomes type 1

T1-SON:

Sonicated transfersomes type 1

T1-EXT:

Extruded transfersomes type 1

T2:

Transfersomes type 2

T2-SON:

Sonicated transfersomes type 2

T2-EXT:

Extruded transfersomes type 2

References

  1. Griffiths CEM, van de Kerkhof P, Czarnecka-Operacz M. Psoriasis and atopic dermatitis. Dermatol Ther (Heidelb). 2017;7(Suppl 1):31–41.

    Article  Google Scholar 

  2. Colombo MD, Cassano N, Bellia G, Vena GA. Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches. ScientificWorldJournal [Internet]. 2013 25 [cited 2019 Feb15]; 2013. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745987/

  3. Freeman DJ. Pharmacology and pharmacokinetics of cyclosporine. Clin Biochem. 1991;24(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  4. Rosmarin DM, Lebwohl M, Elewski BE, Gottlieb AB. National Psoriasis Foundation. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2010;62(5):838–53.

    Article  PubMed  Google Scholar 

  5. Durnian JM, Stewart RM, Tatham R, Batterbury M, Kaye SB. Cyclosporin-A associated malignancy. Clin Ophthalmol. 2007;1(4):421–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Amor KT, Ryan C, Menter A. The use of cyclosporine in dermatology: part I. J Am Acad Dermatol. 2010;63(6):925–46 quiz 947–8.

    Article  CAS  PubMed  Google Scholar 

  7. Lee SS, Tan AWH, Giam YC. Cyclosporin in the treatment of severe atopic dermatitis: a retrospective study. Ann Acad Med Singap. 2004;33(3):311–3.

    CAS  PubMed  Google Scholar 

  8. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61(3):451–85.

    Article  CAS  PubMed  Google Scholar 

  9. Ryan C, Amor KT, Menter A. The use of cyclosporine in dermatology: part II. J Am Acad Dermatol. 2010;63(6):949–72 quiz 973–4.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. van Smeden J, Janssens M, Gooris GS, Bouwstra JA. The important role of stratum corneum lipids for the cutaneous barrier function. Biochim Biophys Acta (BBA) - Mol Cell Biol Lipids. 20141;1841(3):295–313.

  12. Choi HK, Flynn GL, Amidon GL. Percutaneous absorption and dermal delivery of cyclosporin A. J Pharm Sci. 1995;84(5):581–3.

    Article  CAS  PubMed  Google Scholar 

  13. Guo J, Ping Q, Chen Y. Pharmacokinetic behavior of cyclosporin A in rabbits by oral administration of lecithin vesicle and Sandimmun Neoral. Int J Pharm. 2001;216(1–2):17–21.

    Article  CAS  PubMed  Google Scholar 

  14. Lopes LB, Ferreira DA, de Paula D, Garcia MTJ, Thomazini JA, Fantini MCA, et al. Reverse hexagonal phase nanodispersion of monoolein and oleic acid for topical delivery of peptides: in vitro and in vivo skin penetration of cyclosporin A. Pharm Res. 2006;23(6):1332–42.

    Article  CAS  PubMed  Google Scholar 

  15. 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):32–8.

    Article  CAS  PubMed  Google Scholar 

  16. Chen M, Kumar S, Anselmo AC, Gupta V, Slee DH, Muraski JA, et al. Topical delivery of cyclosporine A into the skin using SPACE-peptide. J Control Release. 2015;199:190–7.

    Article  CAS  PubMed  Google Scholar 

  17. Maheshwari RGS, Tekade RK, Sharma PA, Darwhekar G, Tyagi A, Patel RP, et al. Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: a comparative assessment. Saudi Pharm J. 2012;20(2):161–70.

    Article  PubMed  Google Scholar 

  18. Mostafa M, Alaaeldin E, Aly UF, Sarhan HA. Optimization and characterization of thymoquinone-loaded liposomes with enhanced topical anti-inflammatory Activity. AAPS PharmSciTech. 2018;19(8):3490–500.

    Article  CAS  PubMed  Google Scholar 

  19. Fetterly GJ, Straubinger RM. Pharmacokinetics of paclitaxel-containing liposomes in rats. AAPS PharmSci. 2003;5(4):E32.

    Article  PubMed  Google Scholar 

  20. Harel E, Rubinstein A, Nissan A, Khazanov E, Nadler Milbauer M, Barenholz Y, et al. Enhanced transferrin receptor expression by proinflammatory cytokines in enterocytes as a means for local delivery of drugs to inflamed gut mucosa. PLoS One. 2011;6(9):e24202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ghanbarzadeh S, Arami S. Enhanced transdermal delivery of diclofenac sodium via conventional liposomes, ethosomes, and transfersomes. Biomed Res Int. 2013;2013:616810.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kumar R, Dogra S, Amarji B, Singh B, Kumar S, Null S, et al. Efficacy of novel topical liposomal formulation of cyclosporine in mild to moderate stable plaque psoriasis: a randomized clinical trial. JAMA Dermatol. 2016;152(7):807–15.

    Article  PubMed  Google Scholar 

  24. Singh HP, Utreja P, Tiwary AK, Jain S. Elastic liposomal formulation for sustained delivery of colchicine: in vitro characterization and in vivo evaluation of anti-gout activity. AAPS J. 2009;11(1):54–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Abd E, Roberts MS, Grice JE. A comparison of the penetration and permeation of caffeine into and through human epidermis after application in various vesicle formulations. Skin Pharmacol Physiol. 2016;29(1):24–30.

    Article  CAS  PubMed  Google Scholar 

  26. Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta. 1992;1104(1):226–32.

    Article  CAS  PubMed  Google Scholar 

  27. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000;65(3):403–18.

    Article  CAS  PubMed  Google Scholar 

  28. Melero A, Garrigues TM, Almudever P, Villodre AMN, Lehr CM, Schäfer U. Nortriptyline hydrochloride skin absorption: development of a transdermal patch. Eur J Pharm Biopharm. 2008;69(2):588–96.

    Article  CAS  PubMed  Google Scholar 

  29. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56(5):603–18.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Y-T, Shen L-N, Wu Z-H, Zhao J-H, Feng N-P. Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis therapy. Int J Pharm. 2014;471(1–2):449–52.

    Article  CAS  PubMed  Google Scholar 

  31. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics [Internet]. 2018 18 [cited 2019 May 19];10(2). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027495/

  32. Ahad A, Al-Saleh AA, Al-Mohizea AM, Al-Jenoobi FI, Raish M, Yassin AEB, et al. Formulation and characterization of Phospholipon 90 G and tween 80 based transfersomes for transdermal delivery of eprosartan mesylate. Pharm Dev Technol. 2018;23(8):787–93.

    Article  CAS  PubMed  Google Scholar 

  33. Epstein H, Gutman D, Cohen-Sela E, Haber E, Elmalak O, Koroukhov N, et al. Preparation of alendronate liposomes for enhanced stability and bioactivity: in vitro and in vivo characterization. AAPS J. 2008;10(4):505–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. El Maghraby GM, Williams AC, Barry BW. Oestradiol skin delivery from ultradeformable liposomes: refinement of surfactant concentration. Int J Pharm. 2000;196(1):63–74.

    Article  PubMed  Google Scholar 

  36. Isailović BD, Kostić IT, Zvonar A, Đorđević VB, Gašperlin M, Nedović VA, et al. Resveratrol loaded liposomes produced by different techniques. Innovative Food Sci Emerg Technol. 2013;19:181–9.

    Article  CAS  Google Scholar 

  37. Subongkot T, Wonglertnirant N, Songprakhon P, Rojanarata T, Opanasopit P, Ngawhirunpat T. Visualization of ultradeformable liposomes penetration pathways and their skin interaction by confocal laser scanning microscopy. Int J Pharm. 2013;441(1–2):151–61.

    Article  CAS  PubMed  Google Scholar 

  38. Shen L-N, Zhang Y-T, Wang Q, Xu L, Feng N-P. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. Int J Pharm. 2014;460(1–2):280–8.

    Article  CAS  PubMed  Google Scholar 

  39. Tanrıverdi ST, Özer Ö. Novel topical formulations of terbinafine-HCl for treatment of onychomycosis. Eur J Pharm Sci. 2013;48(4–5):628–36.

    Article  PubMed  CAS  Google Scholar 

  40. Sabeti B, Noordin MI, Mohd S, Hashim R, Dahlan A, Javar HA. Development and characterization of liposomal doxorubicin hydrochloride with palm oil. Biomed Res Int. 2014;2014:765426.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Baxa U. Imaging of liposomes by transmission electron microscopy. Methods Mol Biol. 1682;2018:73–88.

    Google Scholar 

  42. Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials. 2000;21(18):1879–85.

    Article  CAS  PubMed  Google Scholar 

  43. Burckart GJ, Venkataramanan R, Ptachcinski RJ, Starzl TE, Griffith BP, Hakala TR, et al. Cyclosporine pharmacokinetic profiles in liver, heart, and kidney transplant patients as determined by high-performance liquid chromatography. Transplant Proc. 1986;18(6 Suppl 5):129–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. USP. Farmacopéicos Validation Procedures, in: United States Pharmacopeia 33. USA: Rockville; 2011. p. 802–5.

    Google Scholar 

  45. Rouser G, Fkeischer S, Yamamoto A. Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids. 1970;5(5):494–6.

    Article  CAS  PubMed  Google Scholar 

  46. Jain S, Jain P, Umamaheshwari RB, Jain NK. Transfersomes--a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev Ind Pharm. 2003;29(9):1013–26.

    Article  CAS  PubMed  Google Scholar 

  47. Zhou W, Liu W, Zou L, Liu W, Liu C, Liang R, et al. Storage stability and skin permeation of vitamin C liposomes improved by pectin coating. Colloids Surf B: Biointerfaces. 2014;117:330–7.

    Article  CAS  PubMed  Google Scholar 

  48. Caddeo C, Díez-Sales O, Pons R, Carbone C, Ennas G, Puglisi G, et al. Cross-linked chitosan/liposome hybrid system for the intestinal delivery of quercetin. J Colloid Interface Sci. 2016;461:69–78.

    Article  CAS  PubMed  Google Scholar 

  49. Chen C, Han D, Cai C, Tang X. An overview of liposome lyophilization and its future potential. J Control Release. 2010;142(3):299–311.

    Article  CAS  PubMed  Google Scholar 

  50. Stark B, Pabst G, Prassl R. Long-term stability of sterically stabilized liposomes by freezing and freeze-drying: effects of cryoprotectants on structure. Eur J Pharm Sci. 2010;41(3–4):546–55.

    Article  CAS  PubMed  Google Scholar 

  51. Kligman AM, Christophers E. Preparation of isolated sheets of human stratum corneum. Arch Dermatol. 1963;88:702–5.

    Article  CAS  PubMed  Google Scholar 

  52. Mathes C, Melero A, Conrad P, Vogt T, Rigo L, Selzer D, et al. Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects. J Control Release. 2016;223:207–14.

    Article  CAS  PubMed  Google Scholar 

  53. Sinico C, Manconi M, Peppi M, Lai F, Valenti D, Fadda AM. Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle-skin interaction. J Control Release. 2005;103(1):123–36.

    Article  CAS  PubMed  Google Scholar 

  54. Melero A, Ferreira Ourique A, Stanisçuaski Guterres S, Raffin Pohlmann A, Lehr C-M, Ruver Beck RC, et al. Nanoencapsulation in lipid-core nanocapsules controls mometasone furoate skin permeability rate and its penetration to the deeper skin layers. Skin Pharmacol Physiol. 2014;27(4):217.

    Article  CAS  PubMed  Google Scholar 

  55. Ourique AF, Melero A, de Bona da Silva C, Schaefer UF, Pohlmann AR, Guterres SS, et al. Improved photostability and reduced skin permeation of tretinoin: development of a semisolid nanomedicine. Eur J Pharm Biopharm. 2011;79(1):95–101.

    Article  CAS  PubMed  Google Scholar 

  56. Zhang Q, Li P, Roberts MS. Maximum transepidermal flux for similar size phenolic compounds is enhanced by solvent uptake into the skin. J Control Release. 2011;154(1):50–7.

    Article  CAS  PubMed  Google Scholar 

  57. Hinna A, Steiniger F, Hupfeld S, Stein P, Kuntsche J, Brandl M. Filter-extruded liposomes revisited: a study into size distributions and morphologies in relation to lipid-composition and process parameters. J Liposome Res. 2016;26(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  58. Castoldi A, Herr C, Niederstraßer J, Labouta HI, Melero A, Gordon S, et al. Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections. Eur J Pharm Biopharm. 2017;118:62–7.

    Article  CAS  PubMed  Google Scholar 

  59. Silva R, Ferreira H, Little C, Cavaco-Paulo A. Effect of ultrasound parameters for unilamellar liposome preparation. Ultrason Sonochem. 2010;17(3):628–32.

    Article  CAS  PubMed  Google Scholar 

  60. Chen M, Liu X, Fahr A. Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application. Int J Pharm. 2011;408(1–2):223–34.

    Article  CAS  PubMed  Google Scholar 

  61. Putri DCA, Dwiastuti R, Marchaban M, Nugroho AK. Optimization of mixing temperature and sonication duration in liposome preparation. J Pharm Sci Commun. 2017;14(2):79–85.

    Article  Google Scholar 

  62. Badran M. Formulation and in vitro evaluation of flufenamic acid loaded deformable liposomes for improved skin delivery. Digest J Nanomater Biostruct. 2014;9:83–91.

    Google Scholar 

  63. Abdulbaqi IM, Darwis Y, Assi RA, Khan NAK. Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation. Drug Des Devel Ther. 2018;12:795–813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Iqbal MA, Md S, Sahni KJ, Baboota S, Dang S, Ali K. Naostructured lipid carriers system: recent advances in drug delivery. J Drug Target. 2012;20(10):813–30.

    Article  CAS  PubMed  Google Scholar 

  65. Duangjit S, Opanasopit P, Rojanarata T, Ngawhirunpat T. Characterization and in vitro skin permeation of meloxicam-loaded liposomes versus transfersomes. J Drug Deliv 2011;2011:418316.

  66. Dubey V, Mishra D, Nahar M, Jain V, Jain NK. Enhanced transdermal delivery of ananti-HIV agent via ethanolic liposomes. Nanomedicine. 2010;6(4):590–6.

    Article  CAS  PubMed  Google Scholar 

  67. Alavi M, Karimi N, Safaei M. Application of various types of liposomes in drug delivery systems. Adv Pharm Bull. 2017;7(1):3–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Emami S, Azadmard-Damirchi S, Peighambardoust SH, Valizadeh H, Hesari J. Liposomes as carrier vehicles for functional compounds in food sector. J Exp Nanosci. 2016;11(9):737–59.

    Article  CAS  Google Scholar 

  69. Khale A. Lipid characterization study in preparation of liposomes of salbutamol sulphate. J Pharm Res. 2011;(4):3.

  70. Venuri S, Yu C, DeGroot JS, Wangsatornthnakun V, Venkat-aram S. Effect of sugars on freeze-thaw and lyophilizationof liposomes. Drug Dev Ind Pharm. 1991;17:327–48.

    Article  Google Scholar 

  71. Garvey CJ, Lenné T, Koster KL, Kent B, Bryant G. Phospholipid membrane protection by sugar molecules during dehydration—insights into molecular mechanisms using scattering techniques. Int J Mol Sci 2013;14(4):8148–8163.

  72. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9:165–9.

    Article  CAS  PubMed  Google Scholar 

  73. Dreier J, Sørensen JA, Brewer JR. Superresolution and fluorescence dynamics evidence reveal that intact liposomes do not cross the human skin barrier. PLoS One. 2016;11(1):e0146514.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Bragagni M, Mennini N, Maestrelli F, Cirri M, Mura P. Comparative study of liposomes, transfersomes and ethosomes as carriers for improving topical delivery of celecoxib. Drug Deliv. 2012;19(7):354–61.

    Article  CAS  PubMed  Google Scholar 

  75. Ascenso A, Raposo S, Batista C, Cardoso P, Mendes T, Praça FG, et al. Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. Int J Nanomedicine. 2015;10:5837–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 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.

    Article  CAS  PubMed  Google Scholar 

  77. Romero EL, Morilla MJ. Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations. Int J Nanomedicine. 2013;8:3171–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Jain S, Umamaheshwari RB, Bhadra D, Jain NK. Ethosomes: a novel vesicular carrier for enhanced transdermal delivery of an AntiHIV agent. Indian J Pharm Sci 2004;66(1):72.

  79. Liu H, Li S, Wang Y, Yao H, Zhang Y. Effect of vehicles and enhancers on the topical delivery of cyclosporin A. Int J Pharm. 2006;311(1–2):182–6.

    Article  CAS  PubMed  Google Scholar 

  80. Verma DD, Fahr A. Synergistic penetration enhancement effect of ethanol and phospholipids on the topical delivery of cyclosporin A. J Control Release. 2004;97(1):55–66.

    Article  CAS  PubMed  Google Scholar 

  81. Benigni M, Pescina S, Grimaudo MA, Padula C, Santi P, Nicoli S. Development of microemulsions of suitable viscosity for cyclosporine skin delivery. Int J Pharm. 2018;545(1–2):197–205.

    Article  CAS  PubMed  Google Scholar 

  82. Aggarwal N, Goindi S. Preparation and evaluation of antifungal efficacy of griseofulvin loaded deformable membrane vesicles in optimized guinea pig model of microsporum canis--dermatophytosis. Int J Pharm. 2012;437(1–2):277–87.

    Article  CAS  PubMed  Google Scholar 

  83. Alvarez-Figueroa MJ, Abarca-Riquelme JM, González-Aramundiz JV. Influence of protamine shell on nanoemulsions as a carrier for cyclosporine—a skin delivery. Pharm Dev Technol. 2019;24(5):630–8.

    Article  CAS  PubMed  Google Scholar 

  84. Hussain A, Haque MW, Singh SK, Ahmed FJ. Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II. Drug Deliv. 2016;23(4):1242–53.

    Article  CAS  PubMed  Google Scholar 

  85. Saoji SD, Atram SC, Dhore PW, Deole PS, Raut NA, Dave VS. Influence of the component excipients on the quality and functionality of a transdermal film formulation. AAPS PharmSciTech. 2015;16(6):1344–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Brandl M. Liposomes as drug carriers: a technological approach. Biotechnol Annu Rev. 2001;7:59–85.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dra. Isabel Moreno, the surgery team and skin donors.

Funding

The authors would like to thank the Spanish Ministry of Economy and Competitiveness-FEDER (SAF2017-85806-R) and the Conselleria d’Educacio, Cultura i Esport of the Generalitat Valenciana “Proyecto Emergente GV2015-054”, which supported this work.

Author information

Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Avenida Vicente Andres Estelles SN, 46100, Burjassot, Valencia, Spain

    Juan J Carreras, Willian E Tapia-Ramirez, Adrian Sala, Antonio J Guillot, Teresa M Garrigues & Ana Melero

Authors
  1. Juan J Carreras
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Willian E Tapia-Ramirez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adrian Sala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio J Guillot
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Teresa M Garrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Melero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Melero.

Ethics declarations

The skin permeability study was approved by the Ethical Committee of the University of Valencia, under the protocol number: H1381683846659. Abdominal skin was obtained from female patients, after signed informed consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 146853 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carreras, J.J., Tapia-Ramirez, W.E., Sala, A. et al. Ultraflexible lipid vesicles allow topical absorption of cyclosporin A. Drug Deliv. and Transl. Res. 10, 486–497 (2020). https://doi.org/10.1007/s13346-019-00693-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-019-00693-4

Keywords

Search

Navigation