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Lanolin-based organogel of salicylic acid: evidences of better dermatokinetic profile in imiquimod-induced keratolytic therapy in BALB/c mice model

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Abstract

The primary aim of the present study was to develop lanolin-based organogel with enhanced delivery potential and reduced skin irritation for the treatment of hyperkeratotic lesions and scaling. The drug was encapsulated in the lipidic bilayers of organogel. The values of particle size, polydispersity index (PDI), and zeta potential of the developed carrier system was found to be 257.5 nm, 0.272, and −24.9 mV, respectively. The system was pseudoplastic in nature with the yield value of 2.3078 Pa. The skin permeation studies exhibited superiority of the prepared lanolin-based organogel formulation over the conventional gel formulation (CGF). Further, the dermatokinetic studies also confirmed better permeation and enhanced skin bioavailability of SA to epidermis as well as dermis vis-à-vis the CGF. In conclusion, the developed organogel system not only improved the delivery profile of SA but also reduced the skin irritant potential. The current findings can provide a suitable alternative for the development of an effective topical formulation of SA for the treatment of hyperkeratotic lesions.

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References

  1. Dougados M. Why and how to use NSAIDs in osteoarthritis. J Cardiovasc Pharmacol. 2006;47:49–54.

    Article  Google Scholar 

  2. Rubin L. Hyperkeratosis in response to mechanical irritation. J Investig Dermatol. 1949;13:313–5.

    Article  CAS  PubMed  Google Scholar 

  3. Baden HP, Alper JC. A keratolytic gel containing salicylic acid in propylene glycol. J Invest Dermatol. 1973;61:330–3.

    Article  CAS  PubMed  Google Scholar 

  4. Bikowski J. Hyperkeratosis of the heels: treatment with salicylic acid in a novel delivery system. Skinmed. 2004;3:350–1.

    Article  PubMed  Google Scholar 

  5. Nordström FL, Rasmuson ÅC. Solubility and melting properties of salicylic acid. J Chem Eng Data. 2006;51:1668–71.

    Article  Google Scholar 

  6. Simmonite N, Lang L, West S, Day S. Salicylic acid in the treatment of corns. Foot. 1994;4:145–50.

    Article  Google Scholar 

  7. Nour SA, Badawi AA, Sakran WS, El-Mancy SMS. Preparation and evaluation of microemulsion systems containing salicylic acid. AAPS PharmSciTech. 2009;10:1081–4.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Moore DJ, Mateus R, Hadgraft J, Lane ME. Percutaneous absorption of salicylic acid—in vitro and in vivo studies. Int J Pharm. 2014;475:471–4.

    Article  PubMed  Google Scholar 

  9. Gupta M, Agrawal U, Vyas SP. Nanocarrier-based topical drug delivery for the treatment of skin diseases. Expert Opin Drug Deliv. 2012;9:783–804.

    Article  CAS  PubMed  Google Scholar 

  10. Pandey M, Belgamwar V, Gattani S, Surana S, Tekade A. Pluronic lecithin organogel as a topical drug delivery system. Drug Deliv. 2010;17:38–47.

    Article  CAS  PubMed  Google Scholar 

  11. Kumar R, Katare OP. Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review. AAPS PharmSciTech. 2005;6:E298–310.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Vintiloiu A, Leroux JC. Organogels and their use in drug delivery—a review. J Control Release. 2008;125:179–92.

    Article  CAS  PubMed  Google Scholar 

  13. Murdan S. Organogels in drug delivery. Expert opinion on drug delivery. 2005;2:489–505.

    Article  CAS  PubMed  Google Scholar 

  14. Sagiri SS, Behera B, Pal K, Basak P. Lanolin-based organogels as a matrix for topical drug delivery. J Appl Polym Sci. 2013;128:3831–9.

    Article  CAS  Google Scholar 

  15. Sahoo S, Kumar N, Bhattacharya C, Sagiri S, Jain K, Pal K, et al. Organogels: properties and applications in drug delivery. Designed monomers and polymers. 2011;14:95–108.

    Article  CAS  Google Scholar 

  16. Katare OP, Kumar R. Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review. AAPS PharmSciTech. 2005;6:E298–310.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Singh N, Khullar N, Kakkar V, Kaur IP. Sesamol loaded solid lipid nanoparticles: a promising intervention for control of carbon tetrachloride induced hepatotoxicity. BMC Complement Altern Med. 2015;15:142.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Raza K, Singh B, Mahajan A, Negi P, Bhatia A, Katare OP. Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin. J Drug Target. 2011;19:293–302.

    Article  CAS  PubMed  Google Scholar 

  19. Bhatia A, Singh B, Raza K, Wadhwa S, Katare OP. Tamoxifen-loaded lecithin organogel (LO) for topical application: development, optimization and characterization. Int J Pharm. 2013;444:47–59.

    Article  CAS  PubMed  Google Scholar 

  20. Chhibber T, Wadhwa S, Chadha P, Sharma G, Katare OP. Phospholipid structured microemulsion as effective carrier system with potential in methicillin sensitive Staphylococcus aureus (MSSA) involved burn wound infection. J Drug Target. 2015;1-10

  21. Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm. 2003;258:141–51.

    Article  CAS  PubMed  Google Scholar 

  22. Yap KL, Liu X, Thenmozhiyal JC, Ho PC. Characterization of the 13-cis-retinoic acid/cyclodextrin inclusion complexes by phase solubility, photostability, physicochemical and computational analysis. Eur J Pharm Sci. 2005;25:49–56.

    Article  CAS  PubMed  Google Scholar 

  23. Upadhyay KK, Tiwari C, Khopade AJ, Bohidar HB, Jain SK. Sorbitan ester organogels for transdermal delivery of sumatriptan. Drug Dev Ind Pharm. 2007;33:617–25.

    Article  CAS  PubMed  Google Scholar 

  24. Bhatia A, Raza K, Singh B, Katare OP. Phospholipid-based formulation with improved attributes of coal tar. J Cosmet Dermatol. 2009;8:282–8.

    Article  PubMed  Google Scholar 

  25. Patel J, Garala K, Basu B, Raval M, Dharamsi A. Solubility of aceclofenac in polyamidoamine dendrimer solutions. Int J Pharma Investig. 2011;1(3):135–8.

    Article  CAS  Google Scholar 

  26. Basu S, Shivhare US, Raghavan GSV. Time dependent rheological characteristics of pineapple jam. Int J Food Eng. 2007;3(3):1–10.

    Article  Google Scholar 

  27. Agarwal R, Katare OP, Vyas SP. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int J Pharm. 2001;228:43–52.

    Article  CAS  PubMed  Google Scholar 

  28. Sharma G, Dhankar G, Thakur K, Raza K, Katare OP. Benzyl benzoate-loaded microemulsion for topical applications: enhanced dermatokinetic profile and better delivery promises. AAPS PharmSciTech. 2016;17:1221–31.

    Article  CAS  PubMed  Google Scholar 

  29. Guth K, Schafer-Korting M, Fabian E, Landsiedel R, van Ravenzwaay B. Suitability of skin integrity tests for dermal absorption studies in vitro. Toxicol in Vitro. 2015;29:113–23.

    Article  CAS  PubMed  Google Scholar 

  30. Sharma G, Kaur M, Raza K, Thakura K, Katare O. Aceclofenac–β-cyclodextrin-vesicles: a dual carrier approach for skin with enhanced stability, efficacy and dermatokinetic profile. RSC Adv. 2016;6:20713–27.

    Article  CAS  Google Scholar 

  31. N'Dri-Stempfer B, Navidi WC, Guy RH, Bunge AL. Improved bioequivalence assessment of topical dermatological drug products using dermatopharmacokinetics. Pharm Res. 2009;26:316–28.

    Article  PubMed  Google Scholar 

  32. Pershing LK, Nelson JL, Corlett JL, Shrivastava SP, Hare DB, Shah VP. Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products. J Am Acad Dermatol. 2003;48:740–51.

    Article  PubMed  Google Scholar 

  33. Raza K, Katare OP, Setia A, Bhatia A, Singh B. Improved therapeutic performance of dithranol against psoriasis employing systematically optimized nano-emulsomes. J Microencapsul. 2013;30:225–36.

    Article  CAS  PubMed  Google Scholar 

  34. Negi P, Singh B, Sharma G, Katare OP. Enhanced topical delivery of lidocaine via ethosomes-based hydrogel: ex-vivo and In-vivo evaluation. J Nanopharm Drug Deliv. 2014;2:1–10.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  36. Negi P, Singh B, Sharma G, Beg S, Katare OP. Biocompatible lidocaine and prilocaine loaded-nanoemulsion system for enhanced percutaneous absorption: QbD-based optimisation, dermatokinetics and in vivo evaluation. J Microencapsul. 2015;32:419–31.

    Article  CAS  PubMed  Google Scholar 

  37. ICH, Q1A(R2). Stability testing of new drug substances and products, In: International conference on harmonisation, IFPMA, Geneva, 2003.

  38. Raza K, Shareef MA, Singal P, Sharma G, Negi P, Katare OP. Lipid-based capsaicin-loaded nano-colloidal biocompatible topical carriers with enhanced analgesic potential and decreased dermal irritation. J Liposome Res. 2014;24:290–6.

    Article  CAS  PubMed  Google Scholar 

  39. Raza K, Singh B, Lohan S, Sharma G, Negi P, Yachha Y, et al. Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity. Int J Pharm. 2013;456:65–72.

    Article  CAS  PubMed  Google Scholar 

  40. Yoo JK, Choo YK, Kwak DH, Lee JM, Lim CY, Lee JH, et al. Protective effects of agonistic anti-4-1BB antibody on the development of imiquimod-induced psoriasis-like dermatitis in mice. Immunol Lett. 2016;178:131–9.

    Article  CAS  PubMed  Google Scholar 

  41. Christensen TE, Callis KP, Papenfuss J, Hoffman MS, Hansen CB, Wong B, et al. Observations of psoriasis in the absence of therapeutic intervention identifies two unappreciated morphologic variants, thin-plaque and thick-plaque psoriasis, and their associated phenotypes. J Invest Dermatol. 2006;126:2397–403.

    Article  CAS  PubMed  Google Scholar 

  42. Amarji B, Garg NK, Singh B, Katare OP. Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics. J Drug Target. 2016;24:147–60.

    Article  CAS  PubMed  Google Scholar 

  43. Sakai K, Sanders KM, Youssef MR, Yanushefski KM, Jensen L, Yosipovitch G, et al. Mouse model of imiquimod-induced psoriatic itch. Pain. 2016;157:2536–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet. 2012;380:738–46. doi:10.1016/S0140-6736(12)60642-4. Epub 2012 Jun 29

    Article  CAS  PubMed  Google Scholar 

  45. van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182:5836–45.

    Article  PubMed  Google Scholar 

  46. Pal K, Banthia A, Majumdar D. Polyvinyl alcohol—gelatin patches of salicylic acid: preparation, characterization and drug release studies. J Biomater Appl. 2006;21:75–91.

    Article  CAS  PubMed  Google Scholar 

  47. Kostarelos K, Luckham PF, Tadros TF. Steric stabilisation of phospholipid vesicles by block copolymers: vesicle flocculation and osmotic swelling caused by monovalent and divalent cations. J Chem Soc Faraday Tran. 1998;94:91–145.

    Google Scholar 

  48. Jatav MP, Ramteke S. Formulation and evaluation of lecithin organogel for treatment of arthritis. International Journal of Scientific World. 2015;3:267–74.

    Article  Google Scholar 

  49. Doukas AG, Soukos NS, Babusis S, Appa Y, Kollias N. Fluorescence excitation spectroscopy for the measurement of epidermal proliferation. Photochem Photobiol. 2001;74:96–102.

    Article  CAS  PubMed  Google Scholar 

  50. Ahmed K, Gribbon PN, Jones MN. The application of confocal microscopy to the study of liposome adsorption onto bacterial biofilms. J Liposome Res. 2002;12:285–300.

    Article  CAS  PubMed  Google Scholar 

  51. Bhalerao S, Raje HA. Preparation, optimization, characterization, and stability studies of salicylic acid liposomes. Drug Dev Ind Pharm. 2003;29:451–67.

    Article  CAS  PubMed  Google Scholar 

  52. Hou D, Xie C, Huang K, Zhu C. The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials. 2003;24:1781–5.

    Article  CAS  PubMed  Google Scholar 

  53. Nasr M, Mansour S, Mortada ND, El Shamy AA. Lipospheres as carriers for topical delivery of aceclofenac: preparation, characterization and in vivo evaluation. AAPS PharmSciTech. 2008;9:154–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tunesi S, Anderson M. Influence of chemisorption on the photodecomposition of salicylic acid and related compounds using suspended titania ceramic membranes. J Phys Chem. 1991;95:3399–405.

    Article  CAS  Google Scholar 

  55. Jagdale SC, Khawale PS, Kuchekar BS, Chabukswar AR. Development and evaluation of pluronic lecithin organogel topical delivery of tapentadol. American Journal of Pharmaceutical Sciences and Nanotechnology. 2015;2:1–21.

    Google Scholar 

  56. Kantaria S, Rees GD, Lawrence MJ. Gelatin-stabilised microemulsion-based organogels: rheology and application in iontophoretic transdermal drug delivery. J Control Release. 1999;60:355–65.

    Article  CAS  PubMed  Google Scholar 

  57. Balaguru S, Ramya Devi D, Vedha Hari BN. Organogel: an ideal drug delivery carrier for nonsteroidal anti-inflammatory drugs through topical Route. Int J Pharm Qual Assur. 2015;6:32–7.

  58. Hurler J, Engesland A, Poorahmary Kermany B, Škalko-Basnet N. Improved texture analysis for hydrogel characterization: gel cohesiveness, adhesiveness, and hardness. J Appl Polym Sci. 2012;125:180–8.

    Article  CAS  Google Scholar 

  59. Bhowmick M, Sengodan T. Mechanisms, kinetics and mathematical modelling of transdermal permeation-an updated review. Int J Res Dev Pharm L Sci. 2013;2:636–41.

    Google Scholar 

  60. Leveque N, Makki S, Hadgraft J, Humbert P. Comparison of Franz cells and microdialysis for assessing salicylic acid penetration through human skin. Int J Pharm. 2004;269:323–8.

    Article  CAS  PubMed  Google Scholar 

  61. Sharma G, Kamboj S, Thakur K, Negi P, Raza K, Katare OP. Delivery of thermoresponsive-tailored mixed micellar nanogel of lidocaine and prilocaine with improved dermatokinetic profile and therapeutic efficacy in topical anaesthesia. AAPS PharmSciTech. 2016; doi:10.1208/s12249-016-0561-8.

    Google Scholar 

  62. Dreher F, Walde P, Luisi P, Elsner P. Human skin irritation studies of a lecithin microemulsion gel and of lecithin liposomes. Skin Pharmacol Physiol. 1996;9:124–9.

    Article  CAS  Google Scholar 

  63. Imayama S, Ueda S, Isoda M. Histologic changes in the skin of hairless mice following peeling with salicylic acid. Arch Dermatol. 2000;136:1390–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Authors are thankful to University Grants Commission (UGC), New Delhi, India, for research grant, Psyco Remedies Limited, Ludhiana, India, and M/s Phospholipid GmbH, Nattermannallee, Germany, for the ex-gratis supply of drug and phospholipids.

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Correspondence to OP Katare.

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Sharma, G., Devi, N., Thakur, K. et al. Lanolin-based organogel of salicylic acid: evidences of better dermatokinetic profile in imiquimod-induced keratolytic therapy in BALB/c mice model. Drug Deliv. and Transl. Res. 8, 398–413 (2018). https://doi.org/10.1007/s13346-017-0364-9

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