Abstract
Background
Topical drug delivery offers improved therapeutic effect and reduced systemic adverse effects of the administered compounds.
Objective
The present work was aimed at developing and comparing levocetirizine loaded polymeric nanoparticles and niosomal formulation(s), respectively, against dinitrochlorobenzene-induced atopic dermatitis animal model.
Methods
The niosome and chitosan nanoparticle were developed and evaluated for particle size distribution, drug loading, and entrapment efficiency. The formulations were optimized through Box-Behnken design. The optimized formulations were dispersed in carbopol gel and evaluated for ex vivo permeation, retention, and in vivo studies.
Results
The optimized niosomes and chitosan nanoparticle exhibited a particle size range of 384.4 ± 64.3 nm and 382.7 ± 59.2 nm, drug loading of 18.99 ± 0.02% and 12.2 ± 1.6%, and entrapment efficiency of 46.63 ± 2.12% and 29.6 ± 1.6%, respectively. The permeation and retention studies displayed less permeation and significantly (p < 0.01) high retention percentage of LCZD by OPT-N gel when compared with OPT-CN gel. In in vivo studies revealed that OPT-N significantly (p < 0.05) reduces erythema score (from 3 to 1) and scratching frequency (70–25 scratches/20 min).
Conclusion
OPT-N gel shows high entrapment efficiency and skin retention capacity of the drug along with better topical applicability and higher therapeutic efficacy. The OPT-N also manifested the maximum peripheral action of LCZD against AD as compared with optimized chitosan gel and plain LCZD gel.
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References
Pal RR, Parashar P, Singh I, Saraf SA. Tamanu oil potentiated novel sericin emulgel of levocetirizine: repurposing for topical delivery against DNCB-induced atopic dermatitis, QbD based development and in vivo evaluation. 2019;36:1–15. https://doi.org/10.1080/02652048.2019.1637474.
Akhtar N, Verma A, Pathak K. Exploring preclinical and clinical effectiveness of nanoformulations in the treatment of atopic dermatitis: safety aspects and patent reviews. Bull Fac Pharm Cairo Univ. 2017;55(1):1–10. https://doi.org/10.1016/j.bfopcu.2016.12.003.
Guttman-Yassky E, Dhingra N, Leung DY. New era of biologic therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013;13(4):549–61. https://doi.org/10.1517/14712598.2013.758708.
Shao M, Hussain Z, Thu HE, Khan S, Katas H, Ahmed TA, et al. Drug nanocarrier, the future of atopic diseases: advanced drug delivery systems and smart management of disease. Colloids Surf B: Biointerfaces. 2016;147:475–91. https://doi.org/10.1016/j.colsurfb.2016.08.027.
Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66(Suppl 1):8–16. https://doi.org/10.1159/000370220.
Snidvongs K, Seresirikachorn K, Khattiyawittayakun L, Chitsuthipakorn W. Sedative effects of Levocetirizine: a systematic review and meta-analysis of randomized controlled studies. Drugs. 2017;77(2):175–86. https://doi.org/10.1007/s40265-016-0682-0.
Goindi S, Kumar G, Kaur A. Novel flexible vesicles based topical formulation of levocetirizine: in vivo evaluation using oxazolone-induced atopic dermatitis in murine model. J Liposome Res. 2014;24(3):249–57. https://doi.org/10.3109/08982104.2014.899365.
Singh N, Parashar P, Tripathi CB, Kanoujia J, Kaithwas G, Saraf SA. Oral delivery of allopurinol niosomes in treatment of gout in animal model. J Liposome Res. 2017;27(2):130–8. https://doi.org/10.1080/08982104.2016.1174943.
Abidin L, Mujeeb M, Imam SS, Aqil M, Khurana D. Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle: quality evaluation and anti-arthritic assessment. Drug Deliv. 2016;23(3):1069–74.
Dong W, Wang X, Liu C, Zhang X, Zhang X, Chen X, et al. Chitosan based polymer-lipid hybrid nanoparticles for oral delivery of enoxaparin. Int J Pharm. 2018;547(1):499–505. https://doi.org/10.1016/j.ijpharm.2018.05.076.
Kalam MA. Development of chitosan nanoparticles coated with hyaluronic acid for topical ocular delivery of dexamethasone. Int J Biol Macromol. 2016;89:127–36. https://doi.org/10.1016/j.ijbiomac.2016.04.070.
Fakhria A, Gilani SJ, Imam SS. Formulation of thymoquinone loaded chitosan nano vesicles: in-vitro evaluation and in-vivo anti-hyperlipidemic assessment. J Drug Deliv Sci Technol. 2019;50:339–46.
Casanova F, Estevinho BN, Santos L. Preliminary studies of rosmarinic acid microencapsulation with chitosan and modified chitosan for topical delivery. Powder Technol. 2016;297:44–9. https://doi.org/10.1016/j.powtec.2016.04.014.
Noor NM, Sheikh K, Somavarapu S, Taylor KMG. Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery. Eur J Pharm Biopharm. 2017;117:372–84. https://doi.org/10.1016/j.ejpb.2017.04.012.
Michailidou G, Christodoulou E, Nanaki S, Barmpalexis P, Karavas E, Vergkizi-Nikolakaki S, et al. Super-hydrophilic and high strength polymeric foam dressings of modified chitosan blends for topical wound delivery of chloramphenicol. Carbohydr Polym. 2019;208:1–13. https://doi.org/10.1016/j.carbpol.2018.12.050.
Solé I, Vílchez S, Miras J, Montanyà N, García-Celma MJ, Esquena J. DHA and l-carnitine loaded chitosan hydrogels as delivery systems for topical applications. Colloids Surf A Physicochem Eng Asp. 2017;525:85–92. https://doi.org/10.1016/j.colsurfa.2017.04.056.
Gibson M. Pharmaceutical preformulation and formulation: a practical guide from candidate drug selection to commercial dosage form. CRC Press; 2016.
Pengnam S, Patrojanasophon P, Rojanarata T, Ngawhirunpat T. Yingyongnarongkul B-e, Radchatawedchakoon W et al. a novel plier-like gemini cationic niosome for nucleic acid delivery. J Drug Deliv Sci Technol. 2019;52:325–33. https://doi.org/10.1016/j.jddst.2019.04.032.
Avadi MR, Sadeghi AM, Mohammadpour N, Abedin S, Atyabi F, Dinarvand R, et al. Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomed Nanotechnol Biol Med. 2010;6(1):58–63. https://doi.org/10.1016/j.nano.2009.04.007.
Kanoujia J, Singh M, Singh P, Saraf SA. Novel genipin crosslinked atorvastatin loaded sericin nanoparticles for their enhanced antihyperlipidemic activity. Mater Sci Eng C. 2016;69:967–76.
Mukherjee B, Patra B, Layek B, Mukherjee A. Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study. Int J Nanomedicine. 2007;2(2):213.
Singh M, Kanoujia J, Singh P, Tripathi CB, Arya M, Parashar P, et al. Development of an α-linolenic acid containing soft nanocarrier for oral delivery: in vitro and in vivo evaluation. RSC Adv. 2016;6(81):77590–602.
Verma J, Kanoujia J, Parashar P, Tripathi CB, Saraf SA. Wound healing applications of sericin/chitosan-capped silver nanoparticles incorporated hydrogel. Drug Deliv Transl Res. 2017;7(1):77–88. https://doi.org/10.1007/s13346-016-0322-y.
Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134(6):1527–34. https://doi.org/10.1038/jid.2013.446.
Siddique MI, Katas H, Jamil A, Amin MCIM, Ng S-F, Zulfakar MH, et al. Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects. Drug Deliv Transl Res. 2019;9(2):469–81.
Yamamoto M, Haruna T, Yasui K, Takahashi H, Iduhara M, Takaki S, et al. A novel atopic dermatitis model induced by topical application with dermatophagoides farinae extract in NC/Nga mice. Allergol Int. 2007;56(2):139–48.
Barbosa AI, Costa Lima SA, Reis S. Development of methotrexate loaded fucoidan/chitosan nanoparticles with anti-inflammatory potential and enhanced skin permeation. Int J Biol Macromol. 2019;124:1115–22. https://doi.org/10.1016/j.ijbiomac.2018.12.014.
Moghddam SRM, Ahad A, Aqil M, Imam SS, Sultana Y. Formulation and optimization of niosomes for topical diacerein delivery using 3-factor, 3-level box-Behnken design for the management of psoriasis. Mater Sci Eng C. 2016;69:789–97. https://doi.org/10.1016/j.msec.2016.07.043.
Imam SS, Aqil M, Akhtar M, Sultana Y, Ali A. Formulation by design-based proniosome for accentuated transdermal delivery of risperidone: in vitro characterization and in vivo pharmacokinetic study. Drug Deliv. 2015;22(8):1059–70.
Rawat D, Tripathi CB, Parashar P, Singh M, Kaithwas G, Saraf SA. Development and characterization of nanostructured lipid carriers of Vetiveria zizanoides oil for therapeutic potential in prickly heat treatment. J Pharm Sci Pharmacol. 2015;2(2):162–71.
Liu X, Shen B, Shen C, Zhong R, Wang X, Yuan H. Nanoparticle-loaded gels for topical delivery of nitrofurazone: effect of particle size on skin permeation and retention. J Drug Deliv Sci Technol. 2018;45:367–72. https://doi.org/10.1016/j.jddst.2018.04.005.
Rehman K, Zulfakar MH. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm. 2014;40(4):433–40.
Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion-based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm. 2006;315(1–2):52–8.
Savin C-L, Popa M, Delaite C, Costuleanu M, Costin D, Peptu CA. Chitosan grafted-poly(ethylene glycol) methacrylate nanoparticles as carrier for controlled release of bevacizumab. Mater Sci Eng C. 2019;98:843–60. https://doi.org/10.1016/j.msec.2019.01.036.
Meng S, Sun L, Wang L, Lin Z, Liu Z, Xi L, et al. Loading of water-insoluble celastrol into niosome hydrogels for improved topical permeation and anti-psoriasis activity. Colloids Surf B: Biointerfaces. 2019;182:110352. https://doi.org/10.1016/j.colsurfb.2019.110352.
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. https://doi.org/10.1016/j.ijpharm.2012.08.015.
Wichayapreechar P, Anuchapreeda S. Dermal targeting of Centella asiatica extract using hyaluronic acid surface modified niosomes. 2019;30:1–11. https://doi.org/10.1080/08982104.2019.1614952.
Chen S, Hanning S, Falconer J, Locke M, Wen J. Recent advances in non-ionic surfactant vesicles (niosomes): fabrication, characterization, pharmaceutical and cosmetic applications. Eur J Pharm Biopharm. 2019;144:18–39. https://doi.org/10.1016/j.ejpb.2019.08.015.
Pradhan S, Moore KM, Ainslie KM. Flexible, microstructured surfaces using chitin-derived biopolymers. 2019;7(35):5328–35. https://doi.org/10.1039/c9tb00965e.
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Pal, R.R., Maurya, A.K., Parashar, P. et al. A Comparative Study of Levocetirizine Loaded Vesicular and Matrix Type System for Topical Application: Appraisal of Therapeutic Potential against Atopic Dermatitis. J Pharm Innov 16, 469–480 (2021). https://doi.org/10.1007/s12247-020-09465-x
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DOI: https://doi.org/10.1007/s12247-020-09465-x