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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Delivery and Anti-Psoriatic Effect of Silibinin-Loaded Polymeric Micelles: An Experimental Study in the Psoriatic Skin Model

Author(s): Fateme Chavoshy, Behzad Sharif Makhmal Zadeh*, Ali Mohammad Tamaddon and Mohammad Houssin Anbardar

Volume 17, Issue 9, 2020

Page: [787 - 798] Pages: 12

DOI: 10.2174/1567201817666200722141807

Price: $65

Abstract

Objective: Psoriasis is an inflamed skin disorder associated with the activation of phosphorylation signals in keratinocytes, which leads to proliferation. Phosphorylation signal inhibitors, such as silibinin can inhibit cell proliferation. Unlike current psoriasis treatment approaches that are associated with dangerous side effects; natural components can introduce new trends in psoriasis treatment. The major problem in the topical treatment of psoriasis is drug localization through the psoriasis lesions.

Methods: In this study, silibinin-loaded polymeric micelles prepared and characterized for drug loading and release and ex vivo permeation through psoriatic and normal mice skin. The optimized batch was used for the treatment of psoriasis lesions in the mice model.

Results: The optimized batch demonstrated mean particle size 18.3 ± 2.1 nm, entrapment efficiency 75.8 ± 5.8%, and prolonged silibinin release. % Silibinin permeated through psoriatic skin after 48 treated by polymeric micelle and aqueous control was 80.35, and 92.6, respectively. Polymeric micelles increased silibinin localization in the psoriatic skin in comparison with control. In psoriatic skin after 7- 10 days treatment by silibinin- loaded polymeric micelle, there was no evidence of psoriasis and the histological evaluation showed no sign of psoriasis. Silibinin-loaded polymeric micelles reduced Psoriasis area index by more than 78% after 14 days.

Conclusion: It seems that polymeric micelles increased the effectiveness of silibinin by drug localization into the psoriatic plaque. Topical STAT- 3inhibitors can be introduced as a new strategy in psoriasis treatment.

Keywords: Silibinin, polymeric micelles, psoriasis, STAT3 inhibitor, mice model, drug localization.

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Graphical Abstract

[1]
Jin, S.P.; Koh, S.J.; Yu, D.A.; Kim, M.W.; Yun, H.T.; Lee, D.H.; Yoon, H.S.; Cho, S.; Park, H.S. Imiquimod-applied interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state. Exp. Dermatol., 2018, 27(1), 43-49.
[http://dx.doi.org/10.1111/exd.13403 ] [PMID: 28677206]
[2]
Sun, J.; Zhao, Y.; Hu, J. Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS One, 2013, 8(6), e67078.
[http://dx.doi.org/10.1371/journal.pone.0067078 ] [PMID: 23825622]
[3]
Hawkes, J.E.; Nguyen, G.H.; Fujita, M.; Florell, S.R.; Callis Duffin, K.; Krueger, G.G.; O’Connell, R.M. microRNAs in psoriasis. J. Invest. Dermatol., 2016, 136(2), 365-371.
[http://dx.doi.org/10.1038/JID.2015.409 ] [PMID: 26802234]
[4]
Pradhan, M.; Singh, D.; Singh, M.R. Novel colloidal carriers for psoriasis: current issues, mechanistic insight and novel delivery approaches. J. Control. Release, 2013, 170(3), 380-395.
[http://dx.doi.org/10.1016/j.jconrel.2013.05.020 ] [PMID: 23770117]
[5]
Sestito, R.; Madonna, S.; Scarponi, C.; Cianfarani, F.; Failla, C.M.; Cavani, A.; Girolomoni, G.; Albanesi, C. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J., 2011, 25(3), 916-927.
[http://dx.doi.org/10.1096/fj.10-172288 ] [PMID: 21098725]
[6]
Andrés, R.M.; Montesinos, M.C.; Navalón, P.; Payá, M.; Terencio, M.C. NF-κB and STAT3 inhibition as a therapeutic strategy in psoriasis: in vitro and in vivo effects of BTH. J. Invest. Dermatol., 2013, 133(10), 2362-2371.
[http://dx.doi.org/10.1038/jid.2013.182 ] [PMID: 23594598]
[7]
Sa, S.M.; Valdez, P.A.; Wu, J.; Jung, K.; Zhong, F.; Hall, L.; Kasman, I.; Winer, J.; Modrusan, Z.; Danilenko, D.M.; Ouyang, W. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J. Immunol., 2007, 178(4), 2229-2240.
[http://dx.doi.org/10.4049/jimmunol.178.4.2229 ] [PMID: 17277128]
[8]
Li, Y.; Song, Y.; Zhu, L.; Wang, X.; Yang, B.; Lu, P.; Chen, Q.; Bin, L.; Deng, L. Interferon kappa is up-regulated in psoriasis and it up-regulates psoriasis-associated cytokines in vivo. Clin. Cosmet. Investig. Dermatol., 2019, 12, 865-873.
[http://dx.doi.org/10.2147/CCID.S218243 ] [PMID: 31819584]
[9]
Bosch-Barrera, J.; Menendez, J.A. Silibinin and STAT3: a natural way of targeting transcription factors for cancer therapy. Cancer Treat. Rev., 2015, 41(6), 540-546.
[http://dx.doi.org/10.1016/j.ctrv.2015.04.008 ] [PMID: 25944486]
[10]
Bosch-Barrera, J.; Queralt, B.; Menendez, J.A. Targeting STAT3 with silibinin to improve cancer therapeutics. Cancer Treat. Rev., 2017, 58, 61-69.
[http://dx.doi.org/10.1016/j.ctrv.2017.06.003 ] [PMID: 28686955]
[11]
Kaur, V.; Kumar, M.; Kumar, A.; Kaur, K.; Dhillon, V.S.; Kaur, S. Pharmacotherapeutic potential of phytochemicals: Implications in cancer chemoprevention and future perspectives. Biomed. Pharmacother., 2018, 97, 564-586.
[http://dx.doi.org/10.1016/j.biopha.2017.10.124 ] [PMID: 29101800]
[12]
Cuyàs, E.; Pérez-Sánchez, A.; Micol, V.; Menendez, J.A.; Bosch-Barrera, J. STAT3-targeted treatment with silibinin overcomes the acquired resistance to crizotinib in ALK-rearranged lung cancer. Cell Cycle, 2016, 15(24), 3413-3418.
[http://dx.doi.org/10.1080/15384101.2016.1245249 ] [PMID: 27753543]
[13]
Wu, P.; Wu, D.; Zhao, L.; Huang, L.; Shen, G.; Huang, J.; Chai, Y. Prognostic role of STAT3 in solid tumors: a systematic review and meta-analysis. Oncotarget, 2016, 7(15), 19863-19883.
[http://dx.doi.org/10.18632/oncotarget.7887 ] [PMID: 26959884]
[14]
Kim, S.; Jeon, M.; Lee, J.; Han, J.; Oh, S.J.; Jung, T.; Nam, S.J.; Kil, W.H.; Lee, J.E. Induction of fibronectin in response to epidermal growth factor is suppressed by silibinin through the inhibition of STAT3 in triple negative breast cancer cells. Oncol. Rep., 2014, 32(5), 2230-2236.
[http://dx.doi.org/10.3892/or.2014.3450 ] [PMID: 25175149]
[15]
Rahman, M.; Alam, K.; Gupta, G.; Afzal, M.; Akhter, S. Classical to current approach for treatment of psoriasis: a review. Endocr. Metabol. Immune Disord - Drug Target., 2012, 12(3), 287-302.
[http://dx.doi.org/10.2174/187153012802002901]
[16]
Rahman, M.; Zaki Ahmad, M.; Kazmi, I.; Akhter, S.; Beg, S.; Gupta, G. Insight into the biomarkers as the novel anti-psoriatic drug discovery tool: a contemporary viewpoint. Curr. Drug Discovery Technol., 2012, 9(1), 48-62.
[17]
Jin, Y.; Yamin, L.; Yanze, L. Advances in the pharmaceutical research on the silymarin. Natural Prod. Res. Devel., 2004, 16(2), 185-187.
[18]
Katare, O.P.; 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), 612-621.
[http://dx.doi.org/10.4103/0378-6323.72451 ] [PMID: 21079304]
[19]
Rahman, M.; Akhter, S.; Ahmad, J.; Ahmad, M.Z.; Beg, S.; Ahmad, F.J. Nanomedicine-based drug targeting for psoriasis: potentials and emerging trends in nanoscale pharmacotherapy. Expert Opin. Drug Deliv., 2015, 12(4), 635-652.
[http://dx.doi.org/10.1517/17425247.2015.982088 ] [PMID: 25439967]
[20]
Zhang, Z.; Tsai, PC; Ramezanli, T.; Michniak-Kohen, B.B. Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases. Nanomed. Nanobiotech., 2013, 5(3), 205-218.
[http://dx.doi.org/10.1002/wnan.1211]
[21]
Kilfoyle, B.E.; Sheihet, L.; Zhang, Z.; Laohoo, M.; Kohn, J.; Michniak-Kohn, B.B. Development of paclitaxel-tyrospheres for topical skin treatment. J. Control. Release, 2012, 163(1), 18-24.
[http://dx.doi.org/10.1016/j.jconrel.2012.06.021 ] [PMID: 22732474]
[22]
Lapteva, M.; Mondon, K.; Möller, M.; Gurny, R.; Kalia, Y.N. Polymeric micelle nanocarriers for the cutaneous delivery of tacrolimus: a targeted approach for the treatment of psoriasis. Mol. Pharm., 2014, 11(9), 2989-3001.
[http://dx.doi.org/10.1021/mp400639e ] [PMID: 25057896]
[23]
Lapteva, M.; Santer, V.; Mondon, K.; Patmanidis, I.; Chiriano, G.; Scapozza, L.; Gurny, R.; Möller, M.; Kalia, Y.N. Targeted cutaneous delivery of ciclosporin A using micellar nanocarriers and the possible role of inter-cluster regions as molecular transport pathways. J. Control. Release, 2014, 196, 9-18.
[http://dx.doi.org/10.1016/j.jconrel.2014.09.021 ] [PMID: 25278258]
[24]
Yang, G.; Zhao, Y.; Zhang, Y.; Dang, B.; Liu, Y.; Feng, N. Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo. Int. J. Nanomed., 2015, 10, 6633-6644.
[http://dx.doi.org/10.2147/IJN.S92665 ] [PMID: 26543366]
[25]
Luo, X.; Guan, R.; Chen, X.; Tao, M.; Ma, J.; Zhao, J. Optimization on condition of Epigallocatechin-3-Gallate (EGCG) nanoliposomes by response surface methodology and cellular uptake studies in Caco-2 cells. Nanoscale Res. Lett., 2014, 9(1), 291.
[http://dx.doi.org/10.1186/1556-276X-9-291 ] [PMID: 24959109]
[26]
Makhmalzade, B.S.; Chavoshy, F. Polymeric micelles as cutaneous drug delivery system in normal skin and dermatological disorders. J. Adv. Pharm. Technol. Res., 2018, 9(1), 2-8.
[http://dx.doi.org/10.4103/japtr.JAPTR_314_17 ] [PMID: 29441317]
[27]
Dragicevic, N.; Maibach, H.I. Percutaneous penetration enhancers physical methods in penetration enhancement; Berlin Heidelberg: Springer Berlin, Heidelberg, 2017.
[28]
Mahmud, A.; Xiong, X.B.; Lavasanifar, A. Novel self-associating poly(ethylene oxide)- block -poly(ε-caprolactone) block copolymers with functional side groups on the polyester block for drug delivery. Macromolecule, 2006, 39(26), 9419-9428.
[29]
Taylor, K.M.G.; Morris, R.M. Thermal analysis of phase transition behavior in liposomes. Thermochim. Acta, 1995, 248, 289-301.
[http://dx.doi.org/10.1016/0040-6031(94)01884-J]
[30]
Chetoni, P.; Burgalassi, S.; Monti, D.; Tampucci, S.; Tullio, V.; Cuffini, A.M.; Muntoni, E.; Spagnolo, R.; Zara, G.P.; Cavalli, R. Solid lipid nanoparticles as promising tool for intraocular tobramycin delivery: pharmacokinetic studies on rabbits. Eur. J. Pharm. Biopharm., 2016, 109, 214-223.
[http://dx.doi.org/10.1016/j.ejpb.2016.10.006 ] [PMID: 27789355]
[31]
Costa, P.; Sousa, Lobo. J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci., 2001, 13(2), 123-133.
[http://dx.doi.org/10.1016/S0928-0987(01)00095-1 ] [PMID: 11297896]
[32]
van der Fits, L.; Mourits, S.; Voerman, J.S.; Kant, M.; Boo, L.; Laman, J.D. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol., 2009, 182(9), 5836-45.
[33]
Amarji, B.; Garg, N.K.; Singh, B.; Katare, O.P. Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics. J. Drug Target., 2016, 24(2), 147-160.
[http://dx.doi.org/10.3109/1061186X.2015.1058804 ] [PMID: 26204326]
[34]
Otero, M.E.; van Geel, M.J.; Hendriks, J.C.M.; van de Kerkhof, P.C.; Seyger, M.M.B.; de Jong, E.M.G.J. A pilot study on the Psoriasis Area and Severity Index (PASI) for small areas: presentation and implications of the low PASI score. J. Dermatolog. Treat., 2015, 26(4), 314-317.
[http://dx.doi.org/10.3109/09546634.2014.972316 ] [PMID: 25275934]
[35]
Ahmad, Z.; Shah, A.; Siddiq, M.; Kraatz, H.B. Polymeric micelles as drug delivery vehicles. RSC Advances, 2014, 4(33), 17028-17038.
[http://dx.doi.org/10.1039/C3RA47370H]
[36]
Shankar, G.; Agrawal, Y.K. Formulation and evaluation of polymeric micelles for a poorly absorbed drug. Res. J. Pharm. Biol. Chem. Sci., 2015, 6(3), 1314-1321.
[37]
Yu, J.N.; Zhu, Y.; Wang, L.; Peng, M.; Tong, S.S.; Cao, X.; Qiu, H.; Xu, X.M. Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol. Sin., 2010, 31(6), 759-764.
[http://dx.doi.org/10.1038/aps.2010.55 ] [PMID: 20523347]
[38]
Miller, T.; van Colen, G.; Sander, B.; Golas, M.M.; Uezguen, S.; Weigandt, M.; Goepferich, A. Drug loading of polymeric micelles. Pharm. Res., 2013, 30(2), 584-595.
[http://dx.doi.org/10.1007/s11095-012-0903-5 ] [PMID: 23135819]
[39]
Bolgen, N. Biodegradable polymeric micelles for drug delivery applications. Stimuli responsive polymeric nanocarrieres for drug delivery applications. Makhloud, A.S.; Nou-Thabit, N., Eds.; Woodheed Publisher,, 2018, Vol. 1, pp. 635-651.
[http://dx.doi.org/10.1016/B978-0-08-101997-9.00027-8 ]
[40]
Bachhav, Y.G.; Mondon, K.; Kalia, Y.N.; Gurny, R.; Möller, M. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals. J. Control. Release, 2011, 153(2), 126-132.
[http://dx.doi.org/10.1016/j.jconrel.2011.03.003 ] [PMID: 21397643]
[41]
Alessandrini, F.; Pfister, S.; Kremmer, E.; Gerber, J.K.; Ring, J.; Behrendt, H. Alterations of glucosylceramide-beta-glucosidase levels in the skin of patients with psoriasis vulgaris. J. Invest. Dermatol., 2004, 123(6), 1030-1036.
[http://dx.doi.org/10.1111/j.0022-202X.2004.23469.x ] [PMID: 15610510]
[42]
Makhmalzadeh, B.S.; Molavi, O.; Vakili, M.R.; Zhang, H.F.; Solimani, A.; Abyaneh, H.S.; Loebenberg, R.; Lai, R.; Lavasanifar, A. Functionalized caprolactone-polyethylene glycol based thermo-responsive hydrogels of silibinin for the treatment of malignant melanoma. J. Pharm. Pharm. Sci., 2018, 21(1), 143-159.
[http://dx.doi.org/10.18433/jpps29726 ] [PMID: 29789104]
[43]
Lin, Y.K.; Yang, S.H.; Chen, C.C.; Kao, H.C.; Fang, J.Y. Using imiquimod-induced psoriasis-like skin as a model to measure the skin penetration of anti-psoriatic drugs. PLoS One, 2015, 10(9), e0137890.
[http://dx.doi.org/10.1371/journal.pone.0137890 ] [PMID: 26355594]
[44]
Park, J.H.; Park, Y.J.; Kim, S.K.; Kwon, J.E.; Kang, H.Y.; Lee, E.S.; Choi, J.H.; Kim, Y.C. Histopathological differential diagnosis and seborrheic dermatitis of the scalp. Ann. Dermatol., 2016, 28(4), 427-432.
[http://dx.doi.org/10.5021/ad.2016.28.4.427 ] [PMID: 27489423]
[45]
Zhang, J.Q.; Liu, J.; Li, X.L.; Jasti, B.R. Preparation and characterization of solid lipid nanoparticles containing silibinin. Drug Deliv., 2007, 14(6), 381-387.
[http://dx.doi.org/10.1080/10717540701203034 ] [PMID: 17701527]
[46]
Sajjadiyan, S.Z.; Ghadernejad, H.; Toofani Milani, A.; Mohammadian, M.; Abdolahpour, S.; Taslimi, S. Preparation of silibinin loaded pegylated niosomal nanoparticles and investigation of its effect on MCF-10A human breast cancer cell line. Der. Pharmacia Letter, 2016, 8(16), 70-75.
[47]
Trivedi, R.; Kompella, U.B. Nanomicellar formulations for sustained drug delivery: strategies and underlying principles. Nanomedicine (Lond.), 2010, 5(3), 485-505.
[http://dx.doi.org/10.2217/nnm.10.10 ] [PMID: 20394539]
[48]
Chung, T.W.; Liu, D.Z. Effects of interpenetration of thermo-sensitive gels by crosslinking of chitosan on nasal delivery of insulin in vitro characterization and in vivo study. Carbohydr. Polym., 2010, 82, 316-322.
[http://dx.doi.org/10.1016/j.carbpol.2010.04.068]
[49]
Wei. G., Lu, L.F., Zhong G.R., Ding, J., Lu, W.Y. A probe study on thermo-sensitive in situ gel as carrier of injectable sustained release protein delivery system. Carol. J. Pharm., 2006, 37, 597-601.
[50]
Salimi, A.; Sharif Makhmal Zadeh, B.; Kazemi, M. Preparation and optimization of polymeric micelles as an oral drug delivery system for deferoxamine mesylate: in vitro and ex vivo studies. Res. Pharm. Sci., 2019, 14(4), 293-307.
[http://dx.doi.org/10.4103/1735-5362.263554 ] [PMID: 31516506]
[51]
Zhao, J.; Agarwal, R. Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis, 1999, 20(11), 2101-2108.
[http://dx.doi.org/10.1093/carcin/20.11.2101 ] [PMID: 10545412]
[52]
Miyoshi, K.; Takaishi, M.; Nakajima, K.; Ikeda, M.; Kanda, T.; Tarutani, M.; Iiyama, T.; Asao, N.; DiGiovanni, J.; Sano, S. Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. J. Invest. Dermatol., 2011, 131(1), 108-117.
[http://dx.doi.org/10.1038/jid.2010.255 ] [PMID: 20811392]
[53]
Hung, C.F.; Lin, Y.K.; Zhang, L.W.; Chang, C.H.; Fang, J.Y. Topical delivery of silymarin constituents via the skin route. Acta Pharmacol. Sin., 2010, 31(1), 118-126.
[http://dx.doi.org/10.1038/aps.2009.186 ] [PMID: 20023692]
[54]
Wichit, A.; Tangsumranjit, A.; Pitaksuteepong, T.; Waranuch, N. Polymeric micelles of PEG-PE as carriers of all-trans retinoic acid for stability improvement. AAPS PharmSciTech, 2012, 13(1), 336-343.
[http://dx.doi.org/10.1208/s12249-011-9749-0 ] [PMID: 22274760]
[55]
Bachhav, Y.G.; Mondon, K.; Kalia, Y.N.; Gurny, R.; Moller, M. Novel micelle formulations to increase cutaneous bioavailability of azole anti-fungals. J. Controlled. Release, 2011, 30(2), 126-132.
[56]
Diordievic, J.; Michniak, B.; Uhrich, K.E. Amphiphilic star-like macromolecules as novel carriers for topical delivery of nonsteroidal anti-inflammatory drugs. AAPS PharmSci, 2003, 16(4), E26.
[57]
Rajitha, P.; Shammika, P.; Aiswarya, S.; Gopikrishnan, A.; Rangasamy, J.; Mangalath, S. Chaulmoogra oil-based methotrexate loaded topical nanoemulsion for the treatment of psoriasis. J. Drug Deliv. Sci. Technol., 2019, 49, 463-476.
[http://dx.doi.org/10.1016/j.jddst.2018.12.020]

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