코아 가교 양친성 고분자 나노입자를 이용한 고함량 유용 약물 담지 고분자 나노입자 제조

김나혜; 김주영; Nahae Kim; Juyoung Kim

Applied Chemistry for Engineering, Vol.27, No.1, 26-34, February, 2016

DOI10.14478/ace.2015.1094 Export Citation

코아 가교 양친성 고분자 나노입자를 이용한 고함량 유용 약물 담지 고분자 나노입자 제조

Preparation of Valuable Compounds Encapsulated Polymer Nanoparticles with High Payload Using Core-crosslinked Amphiphilic Polymer Nanoparticles

김나혜, 김주영 ^†

강원대학교 기능소재공학과

Nahae Kim, and Juyoung Kim^†

Department of Materials engineering, Kangwon National University, Samcheok 25913, Korea

E-mail:

초록

본 연구에서는 반응성 비닐기를 가지고 있는 반응성 양친성 고분자 전구체(Reactive Amphiphilic Reactive Polymer Precursor) (RARP)를 이용하여 제조된 소수성 세그먼트들이 가교된 코아 가교 양친성 고분자(Core-crosslinked Amphiphilic Polymer) (CCAP) 나노입자와 나노침전법을 사용하여서 소수성 유용물질을 고함량으로 담지할 수 있는 새로운 공정을 제안하였다. 극성이 각기 다른 유기용매(에탄올, 아세톤, 테트라하이드로퓨란(THF))들과 소수성 세그먼트 분자량이 다른 CCAP를 사용하여서, 모델 유용 약물인 α-tocopherol의 담지 효율, 담지량 및 약물 담지 나노입자의 크기와 안정성 변화를 조사하였다. 소수성 세그먼트 분자량이 큰 CCAP와 소수성 용매인 THF를 용매로 사용한 경우에 가장 높은 유용 약물 담지량, 담지 효율을 나타내는 안정한 나노입자가 형성이 되었다. 즉 CCAP 나노입자들의 물리적 화학적으로 견고한 나노 구조로 인해서 33 wt%의 높은 담지량과 97% 이상의 담지 효율을 가지면서 물속에서 70 nm의 크기의 안정한 유용 약물 담지 고분자 나노입자를 제조할 수 있었다.

In this study, core-crosslinked amphiphilic polymer (CCAP) nanoparticles prepared using a reactive amphiphilic polymer precursor (RARP) were used for preparing some valuable compounds encapsulated polymer nanoparticles with high payload through nanoprecipitation process. Various solvents (acetone, ethanol, and THF) having different polarity and CCAP nanoparticles prepared using different amphiphilicity were used for the preparation of α-tocopherol encapsulated polymer nanoparticles to investigate their effects on the encapsulation efficiency, payload, nanoparticle size, and stability. CCAP dissolved in hydrophobic solvent, THF, could formα-tocopherol encapsulated polymer nanoparticles dispersed in water with the high payload of α-tocopherol and encapsulation efficiency. Because of their physically and chemically robust nano-structure originated from crosslinking of the hydrophobic core, CCAP nanoparticles could encapsulate α-tocopherol with the high payload (33 wt%) and encapsulation efficiency (97%), and form 70 nm-sized stable nanoparticles in water.

Keywords:amphiphilic polymer;nanoparticles;α-tocopherol;nano-encapsulation;nanoprecipitation

[References]

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Jhonson KA, Adv. Drug Deliv. Rev., 26, 3 (1997)
Park SJ, Kim SH, Lee JR, Lee HB, Hong SK, Polym. Korea, 26(3), 326 (2002)
O’Donnell B, McGinity JW, Drug Dev. Rev., 28, 25 (1997)
Takada S, Yamagata Y, Misaki M, Taira K, Kurokawa T, J. Control. Release, 88, 229 (2003)
Bilati U, Allemann E, Doelker E, Eur. J. Pharm. Sci., 24, 67 (2005)
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Husseini GA, Pitt WG, Adv. Drug Deliv. Rev., 60, 1137 (2008)
Zhang JX, Ellsworth K, Ma PX, J. Control. Release, 145, 116 (2010)
Gandhi PJ, Murthy ZVP, J. Chem. Eng. Data, 55(11), 5050 (2010)
Philippe L, Sylviane L, Amelie B, Ruxandra G, Wouter R, Gillian B, Christine V, Int. J. Pharm., 344, 33 (2007)
Kim JY, Shin DH, Ihn KJ, Nam CW, Macromol. Chem. Phys., 203, 2454 (2002)
Kim JY, Shin DH, Ihn KJ, Macromol. Chem. Phys., 206, 794 (2005)
Kim JY, Kim HM, Shin DH, Ihn KJ, Macromol. Chem. Phys., 207, 925 (2006)
Maia J, Santana M, Br. J. Chem. Eng., 21, 1 (2004)
Kim JY, Wainaina J, Kim JH, Shim JK, J. Nanosci. Nanotechnol., 7, 4000 (2007)
Kim J, Wainaina J, Na JS, J. Ind. Eng. Chem., 17(4), 681 (2011)
Zigoneanu IG, Astete CE, Sabliov CM, Nanotechnology, 19, 105606 (2008)
Shea TB, Ortiz D, Nicolosi RJ, Kumar R, Watterson AC, J. Alzh. Dis., 7, 297 (2005)
Byun YJ, Hwang JB, Bang SH, Darby D, Cooksey K, Dawson PL, Park HJ, Whiteside S, LWT-Food Sci. Technol., 44, 24 (2011)

[Referenced By]

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[2] Bell LN, Stability testing of nutraceuticals and functional foods, In: Handbook of nutraceuticls and functional foods, Wildman REC (ed), CRC Press, New York, 501 (2001).

[3] Metha RC, Thanoo BC, Deluca PP, J. Control. Release, 41, 249 (1996)

[4] Brigelius-Flohe R, Traber MG, Faseb J., 13, 1145 (1999)

[5] Yoo SH, Song YB, Chang PS, Lee HG, Int. J. Biol. Macromol., 38, 25 (2006)

[6] Jhonson KA, Adv. Drug Deliv. Rev., 26, 3 (1997)

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[8] O’Donnell B, McGinity JW, Drug Dev. Rev., 28, 25 (1997)

[9] Takada S, Yamagata Y, Misaki M, Taira K, Kurokawa T, J. Control. Release, 88, 229 (2003)

[10] Bilati U, Allemann E, Doelker E, Eur. J. Pharm. Sci., 24, 67 (2005)

[11] Guerrero DQ, Allemann E, Fessi H, Doelker E, Drug Dev. Ind. Pharm., 24, 1113 (1998)

[12] Yoo HS, Choi HK, Park TG, J. Pharm. Sci., 90, 194 (2001)

[13] Edlund U, Albertsson AC, Degradable polymer microspheres for controlled drug delivery, Albertsson, A.-C.(Ed), 157, 67, Degradable Alphatic polyesters, Advances in Polymer Science, Springer-Verlag, Berlin (2002).

[14] Viswanathan NB, Patil SS, Pandit JK, Lele AK, Kulkarni MG, Mashelkar RA, J. Microencapsul., 18(6), 783 (2001)

[15] Chawla JS, Amiji MM, J. Pharm., 249, 127 (2002)

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[17] Yang Y, Hua C, Dong CM, Biomacromolecules, 10(8), 2310 (2009)

[18] Chiellini E, Chiellini EE, Chiellini F, Solaro R, J. Bioact. Compat. Polym., 16, 441 (2001)

[19] Rosler A, Vandermeulen GWM, Klok HA, Adv. Drug Deliv. Rev., 53, 95 (2001)

[20] Letchford K, Burt H, J. Pharm. Biopharm., 65(3), 259 (2007)

[21] Quaglia F, Ostacolo L, De Rosa G, Rotonda MIL, Ammendola M, Nese G, Maglio G, Palumbo R, Vauthier C, Int. J. Pharm., 324(1), 56 (2006)

[22] Husseini GA, Pitt WG, Adv. Drug Deliv. Rev., 60, 1137 (2008)

[23] Zhang JX, Ellsworth K, Ma PX, J. Control. Release, 145, 116 (2010)

[24] Gandhi PJ, Murthy ZVP, J. Chem. Eng. Data, 55(11), 5050 (2010)

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[27] Kim JY, Shin DH, Ihn KJ, Macromol. Chem. Phys., 206, 794 (2005)

[28] Kim JY, Kim HM, Shin DH, Ihn KJ, Macromol. Chem. Phys., 207, 925 (2006)

[29] Maia J, Santana M, Br. J. Chem. Eng., 21, 1 (2004)

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[31] Kim J, Wainaina J, Na JS, J. Ind. Eng. Chem., 17(4), 681 (2011)

[32] Zigoneanu IG, Astete CE, Sabliov CM, Nanotechnology, 19, 105606 (2008)

[33] Shea TB, Ortiz D, Nicolosi RJ, Kumar R, Watterson AC, J. Alzh. Dis., 7, 297 (2005)

[34] Byun YJ, Hwang JB, Bang SH, Darby D, Cooksey K, Dawson PL, Park HJ, Whiteside S, LWT-Food Sci. Technol., 44, 24 (2011)