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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Impact of the Transfersome Delivered Human Growth Hormone on the Dermal Fibroblast Cells

Author(s): Minoo Azimi, Mahvash Khodabandeh*, Abdolkhalegh Deezagi and Fatemeh Rahimi

Volume 20, Issue 14, 2019

Page: [1194 - 1202] Pages: 9

DOI: 10.2174/1389201020666190809120333

Price: $65

Abstract

Objective: Transfersomes are highly flexible vesicles that are capable of passing through pores smaller than their own sizes due to their elastochemical characteristics, and thus play a key role in drug delivery to the skin.

Methods: In this study, we used transdermal delivery of growth hormone-encapsulated transferosomes (F1 and F2) as antiaging strategy, with the resulting effects being subsequently evaluated. The size, distribution and zeta potential of the particles, together with the in vitro skin permeation and biological activity of the growth hormone loaded onto the transfersomes were measured.

Results: The data demonstrated that treatment of fibroblasts with encapsulated hGH increased cell migration, proliferation and collagen I and III gene expression. According to our results, the maximum amount of growth hormone that passes through the skin during a 24 h time period was 489.54 and 248.46 ng/cm3, for the F1 and F2 transfersomes, respectively. In addition, it was determined that F1 formula as the more efficient carrier, showed no toxicity against cells. With regard to fibroblasts, as one of the most important cells involved in collagen synthesis, skin aging and wound healing, concentrations of growth hormone encapsulated in transferosomes that had an effect on fibroblast growth and division, were determined. The results demonstrated that effective concentrations of the encapsulated growth hormone increased the expression of collagen I and collagen III genes.

Conclusion: Furthermore, analyzing the rate of fibroblast cell migration showed that migration increased significantly at 700 ng/ml growth hormone concentrations, as compared to that of the control.

Keywords: Transfersomes, human growth hormone, drug delivery, fibroblast proliferation, skin absorption, transdermal delivery systems, transdermal skin delivery.

Graphical Abstract

[1]
Krause, W. Skin diseases in consequence of endocrine alterations. Aging Male, 2006, 9(2), 81-95.
[http://dx.doi.org/10.1080/13685530600708573]
[2]
Liberman, B.; Cukiert, A. Fisiologia e fisiopatologia do hormônio do crescimento. Fisiologia e fisiopatologia do hormônio do crescimento,, 2004.
[3]
Lobie, P.E.; Breipohl, W.; Lincoln, D.T.; García-Aragón, J.; Waters, M.J. Localization of the growth hormone receptor/binding protein in skin. J. Endocrinol., 1990, 126(3), 467-471.
[http://dx.doi.org/10.1677/joe.0.1260467] [PMID: 2212936]
[4]
Ben-Shlomo, A.; Melmed, S. Skin manifestations in acromegaly. Clin. Dermatol., 2006, 24(4), 256-259.
[http://dx.doi.org/10.1016/j.clindermatol.2006.04.011] [PMID: 16828406]
[5]
Lange, M.; Thulesen, J.; Feldt-Rasmussen, U.; Skakkebaek, N.E.; Vahl, N.; Jørgensen, J.O.; Christiansen, J.S.; Poulsen, S.S.; Sneppen, S.B.; Juul, A. Skin morphological changes in growth hormone deficiency and acromegaly. Eur. J. Endocrinol., 2001, 145(2), 147-153.
[http://dx.doi.org/10.1530/eje.0.1450147] [PMID: 11454509]
[6]
Global Human Growth Hormone Market 2015-2019. . Technavio,, 2014.
[7]
Lapteva, M.; Kalia, Y.N. Microstructured bicontinuous phase formulations: their characterization and application in dermal and transdermal drug delivery. Expert Opin. Drug Deliv., 2013, 10(8), 1043-1059.
[http://dx.doi.org/10.1517/17425247.2013.783008] [PMID: 23600804]
[8]
Xu, B. Microdevice and method for transdermal delivery and sampling of active substances; Google Patents, 2007.
[9]
Al Shuwaili, A.H.; Rasool, B.K.; Abdulrasool, A.A. Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline. Eur. J. Pharm. Biopharm., 2016, 102, 101-114.
[http://dx.doi.org/10.1016/j.ejpb.2016.02.013] [PMID: 26925505]
[10]
Priyanka, K.; Singh, S. A review on skin targeted delivery of bioactives as ultradeformable vesicles: overcoming the penetration problem. Curr. Drug Targets, 2014, 15(2), 184-198.
[http://dx.doi.org/10.2174/1389450115666140113100338] [PMID: 24410447]
[11]
Li, S-S.; Li, G-F.; Liu, L.; Jiang, X.; Zhang, B.; Liu, Z-G. Evaluation of paeonol skin-target delivery from its microsponge formulation: In vitro skin permeation and in vivo microdialysis. Eur. J. Pharm. Sci., 2017, 21, 379-388.
[12]
Song, Y.; Hemmady, K.; Puri, A.; Banga, A.K. Transdermal delivery of human growth hormone via laser-generated micropores. Drug Deliv. Transl. Res., 2018, 8(2), 450-460.
[http://dx.doi.org/10.1007/s13346-017-0370-y] [PMID: 28321676]
[13]
Sivasubramanian, M.; Lee, J.Y.; Kim, K.J.; Saravanakumar, G.; Kang, Y.M.; Park, J.H. Cyclodextrin-based nanocomplexes for sustained delivery of human growth hormone. J. Nanosci. Nanotechnol., 2013, 13(11), 7306-7311.
[http://dx.doi.org/10.1166/jnn.2013.8090] [PMID: 24245248]
[14]
Kassem, M.A.; Aboul-Einien, M.H.; El Taweel, M.M. Dry gel containing optimized felodipine-loaded transferosomes: A promising transdermal delivery system to enhance drug bioavailability. AAPS PharmSciTech, 2018, 19(5), 2155-2173.
[http://dx.doi.org/10.1208/s12249-018-1020-5] [PMID: 29714001]
[15]
Yang, T.; Cui, F-D.; Choi, M-K.; Cho, J-W.; Chung, S-J.; Shim, C-K.; Kim, D.D. Enhanced solubility and stability of PEGylated liposomal paclitaxel: In vitro and in vivo evaluation. Int. J. Pharm., 2007, 338(1-2), 317-326.
[http://dx.doi.org/10.1016/j.ijpharm.2007.02.011] [PMID: 17368984]
[16]
Liu, C.; Chen, Z.; Yu, W.; Zhang, N. Novel cationic 6-lauroxyhexyl lysinate modified poly(lactic acid)-poly(ethylene glycol) nanoparticles enhance gene transfection. J. Colloid Interface Sci., 2011, 354(2), 528-535.
[http://dx.doi.org/10.1016/j.jcis.2010.10.062] [PMID: 21094495]
[17]
Yamabe, K.; Kato, Y.; Onishi, H.; Machida, Y. Potentiality of double liposomes containing salmon calcitonin as an oral dosage form. J. Control. Release, 2003, 89(3), 429-436.
[http://dx.doi.org/10.1016/S0168-3659(03)00160-3] [PMID: 12737845]
[18]
Elsayed, M.M.; Abdallah, O.Y.; Naggar, V.F.; Khalafallah, N.M. Lipid vesicles for skin delivery of drugs: Reviewing three decades of research. Int. J. Pharm., 2007, 332(1-2), 1-16.
[http://dx.doi.org/10.1016/j.ijpharm.2006.12.005] [PMID: 17222523]
[19]
Sadigh, Z-A.; Badiefar, L.; Shakory, R.; Khodabandeh, M.; Toliyat, T.; Azimzadeh, S. Enhancing effect of cyclodextrins on in vitro skin permeation of hGH. Curr. Trends Biotechnol. Pharm., 2010, 4(3), 784-790.
[20]
Haase, H.R.; Ivanovski, S.; Waters, M.J.; Bartold, P.M. Growth hormone regulates osteogenic marker mRNA expression in human periodontal fibroblasts and alveolar bone-derived cells. J. Periodontal Res., 2003, 38(4), 366-374.
[http://dx.doi.org/10.1034/j.1600-0765.2003.00655.x] [PMID: 12828652]
[21]
Lee, S.W.; Kim, S.H.; Kim, J.Y.; Lee, Y. The effect of growth hormone on fibroblast proliferation and keratinocyte migration. J. Plast. Reconstr. Aesthet. Surg., 2010, 63(4), e364-e369.
[http://dx.doi.org/10.1016/j.bjps.2009.10.027] [PMID: 20022575]
[22]
Patel, R.; Singh, S.; Singh, S.; Sheth, N.; Gendle, R. Development and characterization of curcumin loaded transfersome for transdermal delivery. J. Pharm. Sci. Res., 2009, 1(4), 71-81.
[23]
Shirakawa, M.; Isseroff, R.R. Topical negative pressure devices: use for enhancement of healing chronic wounds. Arch. Dermatol., 2005, 141(11), 1449-1453.
[http://dx.doi.org/10.1001/archderm.141.11.1449] [PMID: 16301393]
[24]
Bellucci, S.; Caen, J. Molecular basis of Glanzmann’s Thrombasthenia and current strategies in treatment. Blood Rev., 2002, 16(3), 193-202.
[http://dx.doi.org/10.1016/S0268-960X(02)00030-9] [PMID: 12163005]
[25]
Varani, J.; Dame, M.K.; Rittie, L.; Fligiel, S.E.; Kang, S.; Fisher, G.J.; Voorhees, J.J. Decreased collagen production in chronologically aged skin: Roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am. J. Pathol., 2006, 168(6), 1861-1868.
[http://dx.doi.org/10.2353/ajpath.2006.051302] [PMID: 16723701]
[26]
Barrientos, S.; Stojadinovic, O.; Golinko, M.S.; Brem, H.; Tomic-Canic, M. Growth factors and cytokines in wound healing. Wound Repair Regen., 2008, 16(5), 585-601.
[http://dx.doi.org/10.1111/j.1524-475X.2008.00410.x] [PMID: 19128254]
[27]
Liu, Q.; Deng, S.; Wang, Y. [Mechanism of recombinant human growth hormone accelerating burn wound healing in burn patients. Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi. Chinese J. Burns, 2000, 16(1), 66-77.
[28]
Barenholz, Y. Liposome application: Problems and prospects. Curr. Opin. Colloid Interface Sci., 2001, 6(1), 66-77.
[http://dx.doi.org/10.1016/S1359-0294(00)00090-X]
[29]
Sweetman, S.C. Martindale: The complete drug reference, 37th ed; London, England, UK: Pharmaceutical Press, 2009, pp. 75-76.
[30]
Montanari, J.; Perez, A.P.; Di Salvo, F.; Diz, V.; Barnadas, R.; Dicelio, L.; Doctorovich, F.; Morilla, M.J.; Romero, E.L. Photodynamic ultra-deformable liposomes: Design and characterization. Int. J. Pharm., 2007, 330(1-2), 183-194.
[http://dx.doi.org/10.1016/j.ijpharm.2006.11.015] [PMID: 17157460]
[31]
Wei, C.; Wei, W.; Morris, M.; Kondo, E.; Gorbounov, M.; Tomalia, D.A. Nanomedicine and drug delivery. Med. Clin. North Am., 2007, 91(5), 863-870.
[http://dx.doi.org/10.1016/j.mcna.2007.05.005] [PMID: 17826106]
[32]
Gupta, P.N.; Vyas, S.; Vishwidyalaya, H.S.G. Transfersomes for vaccine delivery: A potential approach for topical immunization. Med. Chem. Res., 2004, 13(6-7), 414-426.
[http://dx.doi.org/10.1007/s00044-004-0045-3]
[33]
Ranzato, E.; Martinotti, S.; Volante, A.; Mazzucco, L.; Burlando, B. Platelet lysate modulates MMP-2 and MMP-9 expression, matrix deposition and cell-to-matrix adhesion in keratinocytes and fibroblasts. Exp. Dermatol., 2011, 20(4), 308-313.
[http://dx.doi.org/10.1111/j.1600-0625.2010.01173.x] [PMID: 20955204]
[34]
Ching, Y-H.; Sutton, T.L.; Pierpont, Y.N.; Robson, M.C.; Payne, W.G. The use of growth factors and other humoral agents to accelerate and enhance burn wound healing. Eplasty, 2011, 11(7)e41
[PMID: 22084646]

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