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Development of Lecithin Organogel to Improve Solubility of Genistein

레시틴 오가노겔을 이용한 난용성 제니스테인의 용해도 향상

  • 이수진 ((주)LG 생활건강 기술연구원) ;
  • 김정아 ((주)LG 생활건강 기술연구원) ;
  • 강내규 ((주)LG 생활건강 기술연구원) ;
  • 박선규 ((주)LG 생활건강 기술연구원) ;
  • 이천구 ((주)LG 생활건강 기술연구원)
  • Received : 2015.09.17
  • Accepted : 2015.09.25
  • Published : 2015.09.30

Abstract

Organogels are semi-solid systems that consist of an apolar solvent as the liquid phase within a three-dimensional networked structure. In this study, we developed a stable and skin penetration-enhanced Lecithin Organogel (LO) containing genistein, which is one of the poorly soluble active ingredients in both polar and apolar phase. After screening of various components (type of gelators, organic and aqueous phase), hydrogenated lecithin (HL), sunflower oil (SO), dipropylene glycol (DPG), and polyethylene glycol (PEG) were mainly used in this formulation. Phase ternary diagram was employed for optimization of the composition in the LO. The formulated LO were evaluated for its organoleptic characteristics, stability, pH, rheology, phase transition temperatures, microscopic analysis and skin penetration. The optimized stable LO system can be utilized as an effective and stable cosmetic formulation that can carry poorly soluble active ingredients at high concentration for topical dermal delivery.

오가노겔은 반고형상이며 3차원의 네트워크 구조로 이루어진 친유성 용매로 이루어져 있다. 본 연구에서는 유상과 수상에서 모두 난용성 특징을 가진 제니스테인을 포함하는 레시틴 오가노겔을 개발하였다. 이 시스템은 안정할 뿐만 아니라 경피 흡수 실험에서도 높은 흡수율을 보였다. 본 오가노겔 제형에 적합한 원료들을 선별한 결과, 수화된 레시틴, 해바라기유, dipropylene glycol (DPG), polyethylene glycol (PEG)이 이 시스템에서 주로 사용되었다. 레시틴 오가노겔의 제조에 적합한 원료의 함량은 phase ternary diagram 작성을 통하여 결정하였다. 제조된 레시틴 오가노겔을 organoleptic characteristics, stability, pH, rheology, phase transition temperatures, microscopic analysis, skin penetration 실험을 통해 평가하였다. 본 연구 결과를 통해 본 논문에서 제시하는 레시틴 오가노겔 제형은 안정한 상태에서 난용성 물질을 높은 농도로 피부에 효과적으로 전달할 수 있는 제형으로 활용될 수 있을 것이라 생각된다.

Keywords

References

  1. D. Locati, S. Morandi, A. Cupisti, L. Ghiadoni, and A. Arnoldi, Characterization and quantification of soy isoflavone metabolites in serum of renal transplanted patients by high-performance liquid chromatography/electrospray ionization mass spectrometry, Rapid Commun. Mass Spectrom., 19(23), 3473 (2005). https://doi.org/10.1002/rcm.2222
  2. W. Huachen, R. Bowen, Q. Cai, S. Barnes, and Y. Wang, Antioxidant and antipromotional effects of the soybean isoflavone genistein, Biol. Med., 208(1), 124 (1995). https://doi.org/10.3181/00379727-208-43844
  3. W. A. Fritz, L. Coward, J. Wang, and C. A. Lamartiniere, Dietary genistein : perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat, Carcinogenesis, 19(12), 2151 (1998). https://doi.org/10.1093/carcin/19.12.2151
  4. M. Jurzak and K. Adamczyk, Drug biochemistry influence of genistein on c-jun, c-fos and fos-b of ap-1 subunits expression in skin keratinocytes, fibroblasts and keloid fibroblasts cultured in vitro, Acta Pol. Pharm., 70(2), 205 (2013).
  5. Z. R. Huang, C. F. Hung, Y. K. Lin, and J. Y. Fang, In vitro and in vivo evaluation of topical delivery and potential dermal use of soy isoflavones genistein and daidzein, Int. J. Pharm., 364(1), 36 (2008). https://doi.org/10.1016/j.ijpharm.2008.08.002
  6. S. R. Georgetti, R. Casagrande, W. Verri, R. F. V. Lopez, and M. J. V. Fonseca, Evaluation of in vivo efficacy of topical formulations containing soybean extract, Int. J. Pharm., 352(1-2), 189 (2008). https://doi.org/10.1016/j.ijpharm.2007.10.037
  7. A. Vintiloiu and J. Leroux, Organogels and their use in drug delivery-a review, J. Control., 125(3), 179 (2008). https://doi.org/10.1016/j.jconrel.2007.09.014
  8. S. Sahooa, N. Kumarb, C. Bhattacharyac, S. S. Sagirid, K. Jaine, K. Palf, and B. Nayak, Organogels: properties and applications in drug delivery, Des. Monomers Polym., 14(2), 95 (2011). https://doi.org/10.1163/138577211X555721
  9. Y. A. Shchipunov and E. Shumilina, Lecithin bridging by hydrogen bonds in the organogel, Mater. Sci. Eng., 3(1), 43 (1995). https://doi.org/10.1016/0928-4931(95)00102-6
  10. Y. A. Shchipunov and E. Shumilina, Lecithin organogels: role of polar solvent and nature of intermolecular interactions, Colloid J. Russ. Acad. Sci., 58(1), 117 (1996).
  11. R. Kumar and O. P. Katare, Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review, AAPS Pharm. Sci. Tech., 6(2), E298 (2005). https://doi.org/10.1208/pt060240
  12. H. Willimann, P. Walde, P. L. Luisi, A. Gazzaniga, and F. troppolo, Lecithin organogel as matrix for transdermal transport of drugs, J. Pharm. Sci., 81(9), 871 (1992). https://doi.org/10.1002/jps.2600810906
  13. D. Grace, J. Rogers, K. Skeith, and K. Anderson, Topical diclofenac versus placebo: a double blind, randomized clinical trial in patients with osteoarthritis of the knee, J. Rheumatol., 26(12), 2659 (1999).
  14. P. Mahler, F. Mahler, H. Duruz, M. Ramazzina, V. Liguori, and G. Mautone, Double-blind, randomized, controlled study on the efficacy and safety of a novel diclofenac epolamine gel formulated with lecithin for the treatment of sprains, strains and contusions, Drugs Exp. Clin., 29(1), 45 (2003).
  15. G. Spacca, A. Cacchio, A. Forgacs, P. Monteforte, and G. Rovetta, Analgesic efficacy of a lecithin-vehiculated diclofenac epolamine gel in shoulder periarthritis and lateral epicondylitis: a placebo-controlled, multicenter, randomized, double-blind clinical trial, Drugs Exp. Clin., 31(4), 147 (2005).
  16. G. Agrawal, M. Juneja, S. Agrawal, S. K. Jain, and S. S. Pancholi, Preparation and characterization of reverse micelle based organogels of piroxicam. Die Pharm. Int. J. Pharm. Sci., 59(3), 191 (2004).
  17. C. Nastruzzi and R. Gambari, Antitumor activity of (trans) dermally delivered aromatic tetra-amidines, J. Control Release., 29(1), 53 (1994). https://doi.org/10.1016/0168-3659(94)90121-X
  18. S. Bhatnagar and S. P. Vyas, Organogel-based system for transdermal delivery of propranolol, J. Microencapsul., 11(4), 431 (1994). https://doi.org/10.3109/02652049409034260
  19. R. Aboofazeli, H. Zia, and T. E. Needham, Transdermal delivery of nicardipine: an approach to in vitro permeation enhancement, Drug Deliv., 9(4), 239 (2002). https://doi.org/10.1080/10717540260397855
  20. I. Shaikh, K. R. Jadhav, P. S. Gide, V. J. Kadam, and S. S. Pisal, Topical delivery of aceclofenac from lecithin organogels: preformulation study, Curr. Drug Deliv., 3(4), 417 (2006). https://doi.org/10.2174/156720106778559010
  21. F. Dreher and E. Wehrli, Interaction of a lecithin microemulsion gel with human stratum corneum and its effect on transdermal transport, J. Control Release., 45(2), 131 (1997). https://doi.org/10.1016/S0168-3659(96)01559-3
  22. D. Satapathy, D. Biswas, B. Behera, S. S. Sagiri, K. Pal, and K. Pramanik, Sunflower-oil-based lecithin organogels as matrices for controlled drug delivery, J. Appl. Polym. Sci., 129(2), 585 (2013). https://doi.org/10.1002/app.38498
  23. N. Baran, V. K. Singh, K. Pal, A. Anis, D. K. Pradhan, and K. Pramanik, Development and characterization of soy lecithin and palm oil-based organogels, Polym. Plast. Technol. Eng., 53(9), 865 (2014). https://doi.org/10.1080/03602559.2013.869600
  24. V. Agrawal, V. Gupta, S. Ramteke, and P. Trivedi, Preparation and evaluation of tubular micelles of pluronic lecithin organogel for transdermal delivery of sumatriptan, AAPS Pharm. Sci. Tech., 11(4), 1718 (2010). https://doi.org/10.1208/s12249-010-9540-7
  25. M. Lescanne, P. Grondin, A. d'Aleo, F. Fages, J.-L. Pozzo, O. Mondain Nonval, P. Reinheimer, and A. Colin, Thixotropic organogels based on a simple N-hydroxyalkyl amide: rheological and aging properties, Langmuir, 20(8), 3032 (2004). https://doi.org/10.1021/la035219g
  26. K. Choi, H. Son, and S. Lee, The effect of glossiness and lattice structure of wax matrixes on using n-parrafin and branched wax, J. Soc. Cosmet. Scientists Korea, 36(2), 99 (2010).
  27. S. F. Taveira, A. Nomizo, and R. F. Lopez, Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicity, J. Control Release, 134(1), 35 (2009). https://doi.org/10.1016/j.jconrel.2008.11.002
  28. A. Bhatia, B. Singh, K. Raza, S. Wadhwa, and O. P. Katare, Tamoxifen-loaded lecithin organogel (LO) for topical application: development, optimization and characterization, Int. J. Pharm., 444(1-2), 47 (2013). https://doi.org/10.1016/j.ijpharm.2013.01.029
  29. J. Varshosaz, S. Andalib, M. Tabbakhian, and N. Ebrahimzadeh, Development of lecithin nanoemulsion based organogels for permeation enhancement of metoprolol through rat skin, J. Nanomater., 2013, 1 (2013).
  30. S. Pradhan, S. S. Sagiri, V. K. Singh, K. Pal, S. S. Ray, and D. K. Pradhan, Palm oil-based organogels and microemulsions for delivery of antimicrobial drugs, J. Appl. Polym. Sci., 131(6), 39979 (2014).
  31. R. Scartazzini and P. L. Luisi, Organogels from lecithins, J. Phys. Chem., 40(2), 829 (1988).
  32. L. M. Andrade, C. de Fatima Reis, L. Maione-Silva, J. Luiz V., A. A. Alonso, R. C. Serpa, R. N. Marreto, E. M. Lima, and S. F. Taveira, Impact of lipid dynamic behavior on physical stability, in vitro release and skin permeation of genistein-loaded lipid nanoparticles, Eur. J. Pharm. Biopharm., 88(1), 40 (2014). https://doi.org/10.1016/j.ejpb.2014.04.015