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미녹시딜과 다이아미노피리미딘옥사이드 성분을 함유하는 니오좀 제형의 물성 및 피부투과

Physical Properties and Skin Penetration of Niosome Formulations Containing Minoxidil and Diaminopyrimidine Oxide

  • 김보경 (제주대학교 화학.코스메틱스학과) ;
  • 김원형 (제주대학교 화학.코스메틱스학과) ;
  • 윤경섭 (제주대학교 화학.코스메틱스학과)
  • Bo Kyung Kim (Department of Chemistry and Cosmetics, College of Natural Science, Jeju National University) ;
  • Won Hyung Kim (Department of Chemistry and Cosmetics, College of Natural Science, Jeju National University) ;
  • Kyung-Sup Yoon (Department of Chemistry and Cosmetics, College of Natural Science, Jeju National University)
  • 투고 : 2023.04.01
  • 심사 : 2023.06.30
  • 발행 : 2023.06.30

초록

본 연구에서는 의약품 원료로 잘 알려진 minoxidil과 화장품 원료인 diaminopyrimidine oxide (DAO) 활성성분으로 사용하여 니오좀(niosome)의 물성평가와 더불어 인공피부에 대한 경피투과율을 비교하였다. 나노입자의 니오좀을 제조하기 위해 고압유화(high pressure homogenization) 방법을 이용하였으며 제타사이저(zetasizer)로 물성평가를 진행하였다. 활성성분을 포함한 니오좀의 입자크기는 HLB에 따라 평균 99 ~ 123 nm, 제타전위(zeta potential)는 -60 ~ -81 mV의 범위로 측정되었다. DSC (differential scanning colorimetry)를 통해 결정성 성분인 minoxidil이 니오좀 내에 무결정 상태로 균일하게 용해되어 있음을 확인하였다. 경피투과량을 확인 및 비교하기 위해 in vitro Franz diffusion cell 방법으로 측정하였으며, 니오좀 제형이 대조군인겔 제형보다 minoxidil의 경우 3.4배, DAO의 경우 11.1배 높은 투과율을 보였다. 또한 minoxidil과 DAO 니오좀의 경피투과 비교 시 유사한 경향을 보였으며, 상대적으로 DAO의 투과량이 많았다. HLB 값을 달리한 니오좀 제형을 Cryo-TEM을 이용하여 형상을 관찰하였으며, 모두 소포체가 형성되었으며 SUV (small unilamella vesicle)와 LUV (large unilamella vesicle)의 중간 형태임을 확인하였다. 본 연구를 통하여 탈모에 효과적인 약물인 minoxidil과 화장품 원료인 DAO 성분을 니오좀 제형에 캡슐화시킴으로써 효과적으로 피부에의 전달을 기대할 수 있다.

In this study, minoxidil, which is well known as a pharmaceutical raw material, and diaminopyrimidine oxide (DAO), which is a cosmetic raw material, were used as active ingredients to evaluate the physical properties of niosomes and compare the skin penetrations of artificial skin. To prepare niosomes of the size of nanoparticles, a high pressure homogenization method was used, and physical properties were evaluated with a zetasizer. The particle size of the noisome including the active ingredient was measured to be 99 to 123 nm according to HLB, and the zeta potential was measured in the range of -60 to -81 mV. Through DSC (differential scanning colorimetry), it was confirmed that minoxidil, a crystalline component, was uniformly dissolved in an amorphous state in niosomes. In order to confirm and compare skin penetration, it was measured by the in vitro Franz diffusion cell method, and the niosome formulation showed 3.4 times higher penetration for minoxidil and 11.1 times higher penetration for DAO than the control gel formulation. In addition, when comparing the skin penetration of minoxidil niosome and DAO niosome, a similar trend was shown, and the penetration amount of DAO was relatively high. The shapes of the niosome formulations with different HLB values were observed using Cryo-TEM, and it was confirmed that vesicles were formed in all of them and that they were intermediate between SUV (small unilamella vesicle) and LUV (large unilamella vesicle). Through this study, minoxidil, an effective drug for hair loss, and DAO, a cosmetic raw material, can be effectively delivered to the skin by encapsulating them in a noisome formulation.

키워드

참고문헌

  1. H. E. Jin, J. H. Kim, and I. Y. Paik, Transdermal drug delivery system, J. Korean Ind. Eng. Chem., 16(1), 15 (2005).
  2. S. K. Dubey, A. Dey, G. Singhvi, M. M. Pandey, V. Singh, and P. Kesharwani, Emerging trends of nanotechnology in advanced cosmetics, Colloids Surf. B, Biointerfaces, 214, 1 (2022).
  3. S. Chen, S. Hanning, J. Falconer, M. Locke, and J. Wen, Recent advances in non-ionic surfactant vesicles (niosomes): Fabrication, characterization, pharmaceutical and cosmetic applications, Eur. J. Pharm. Biopharm., 144(12), 18 (2019).
  4. P. Bhardwaj, P. Tripathi, R. Gupta, and S. Pandey, Niosomes: A review on niosomal research in the last decade, J. Drug Deliv. Sci. Technoi., 56, 1 (2020).
  5. X. Jin, D. A. Streett, C. A. Dunlap, and M. E. Lyn, Application of hydrophilic-lipophilic balance (HLB) number to optimize a compatible non-ionic surfactant for dried aerial conidia of Beauveria bassiana, Biol. Control, 46(2), 226 (2008).
  6. C. Marianecci, L. D. Marzio, F. Rinaldi, C. Celia, D. Paolino, F. Alhaique, S. Esposito, and M. Carafa, Niosomes from 80s to present: The state of the art, Adv. Colloid Interface Sci., 205, 187 (2014).
  7. I. F. Uchegbu and A. T. Florence, Non-ionic surfactant vesicles (Niosome): Physical and pharmaceutical chemistry, Adv. Colloid Interface Sci., 58, 1 (1955).
  8. H. Jousma, J. G. H. Joosten, G. S. Gooris, and H. E. Junginger, Changes of mesophase structure of BRIJ 96/water mixtures on addition of liquid paraffin, Colloid Polym. Sci., 267(4), 353 (1989).
  9. H. Jousma, J. G. H. Joosten, and H. E. Junginger, Mesophases in mixtures of water and polyoxyethylene surfactant: Variations of repeat spacing with temperature and composition, Colloid Polym. Sci., 266(7), 640 (1988).
  10. L. Tavano, P. Alfano, R. Muzzalupo, and B. de Cindio, Niosomes vs microemulsions: New carriers for topical delivery of capsaicin, Colloids Surf. B, Biointerfaces, 87(2), 333 (2011).
  11. L. Basiri, G. Rajabzadeh, and A. Bostan, α-Tocopherol-loaded niosome prepared by heating method and its release behavior, Food Chem., 221, 620 (2017).
  12. P. Garcia-Manrique, N. D. Machado, M. A. Fernandez, M. C. Blanco-Lopeza, M. Matos, and G. Gutierrez, Effect of drug molecular weight on niosomes size and encapsulation efficiency, Colloids Surf. B, Biointerfaces, 186, 1 (2020).
  13. N. B. Mahale, P. D. Thakkar, R. G. Mali, D. R. Walunj, and S. R. Chaudhari, Niosomes: Novel sustained release nonionic stable vesicular systems-An overview, Adv. Colloid Interface Sci., 183-184(15), 46 (2012).
  14. E. Mayhew, R. Lazo, W. J. Vail, J. King, and A. M. Green, Characterization of liposomes prepared using a microemulsifier, Biochim. Biophys. Acta., 775(2), 169 (1984).
  15. M. S. Park, J. K. Park, G. W. Lee, M. K. Baek, and U. K. Jee, Preparation and evaluation of aclarubicin liposome using microfluidizer, Yakhak Hoeji, 42(3), 265 (1998).
  16. A. Laouini, C. Jaafar-Maalej, I. Limayem-Blouza, S. Sfar, C. Charcosset, and H. Fessi, Preparation, characterization and applications of liposome: state of the art, J. Colloid Sci. Biotechnol., 1(2), 147 (2012).
  17. M. Rajabi and S. A. Mousa, Lipid Nanoparticles and their application in nanomedicine, Curr. Pharm. Biotechnol., 17(8), 662 (2016).
  18. A. G. Messenger and J. Rundergren, Minoxidil: mechanisms of action on hair growth, Br. J. Dermatol., 150(2), 186 (2004).
  19. P. Balakrishnan, S. Shanmugam, W. S. Lee, W. M. Lee, J. O. Kim, D. H. Oh, D. D. Kim, J. S. Kim, B. K. Yoo, H. G. Choi, J. S. Woo, and C. S. Yong, Formulation and in vitro assessment of minoxidil noisomes for enhanced skin delivery, Int. J. Pharm., 377(1-2), 1 (2009).
  20. A. Goren and T. Naccarato, Minoxidil in the treatment of androgenetic alopecia, Dermatol. Therapy, 31(5), 1 (2018).
  21. I. Rizwana, K. V. Prakash, and G. K. Mohan, Simultaneous estimation of minoxidil and aminexil in bulk and pharmaceutical formulations by RP-HPLC method, Orient. J. Chem., 31(1), 277 (2015).
  22. M. Masjedi and T. Montahaei, An illustrated review on nonionic surfactant vesicles (niosomes) as an approach in modern drug delivery: Fabrication, characterization, pharmaceutical, and cosmetic applications, J. Drug Deliv. Sci. and Technol., 61, 1 (2021).
  23. S. J. Yang, T. Y. Kim, C. M. Lee, K. S. Lee, and K. S. Yoon, Study on the stability of biotin-containing nano-liposome, J. Soc. Cosmet. Sci. Korea, 46(2), 133 (2020).
  24. Y. P. Patil and S. Jadhav, Novel methods for liposome preparation, Chem. Phys. Lipids., 177, 8 (2013).
  25. H. S. Jeon, E. S. Jo, M. S. Kim, M. H. Kang, D. H. Oh, and S. K. Lee, A retinyl palmitate-loaded solid lipid nanoparticle system: Effect of surface modification with dicetyl phosphate on skin permeation in vitro and anti-wrinkle effect in vivo, Int. J. Pharm., 452(1-2), 311 (2013).
  26. S. Uprit, R. K. Sahu, A. Roy, and A. Pare, Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia, Saudi Pharm. J., 21(4), 379 (2013).
  27. M. Aranya, W. Paveena, M. Jiradej, S. Hideki, S. Fumio, Y. Makoto, and A. Masahiko, Characterization of vesicles preparred with various non-ionic surfactants mixed with cholesterol, Colloids Surf. B, Biointerfaces, 30(1-2), 129 (2003).
  28. B. K. Kim, Master's Thesis Dissertation, Jeju National Univ., Jeju, Korea (2022).
  29. N. Mali, S. Darandale, and P. Vavia, Niosomes as a vesicular carrier for topicaladministration of minoxidil: formulation and in vitroassessment, Drug Deliv. Transl. Res., 3(6), 587 (2013).
  30. Y. Morteza, H. Azadeh, B. Noushin, S. Soraya, and D. Simin, The Impact of surfactant composition and surface charge of niosomes on the oral absorption of repaglinide as a BCS II model drug, Int. J. Nanomedicine, 15, 8767 (2020).