Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Polymer Effects on Appetite Suppression by Lipoic Acid Nanoparticles

리포익산 나노 입자의 식욕 억제에 대한 고분자의 영향

  • Choi, Hye-Min (Department of Chemical Engineering and Materials Science, Chung-Ang University) ;
  • Park, Chul-Ho (Department of Chemical Engineering and Materials Science, Chung-Ang University) ;
  • Lee, Ki-Up (Department of Internal Medicine and Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Park, Joong-Yeol (Department of Internal Medicine and Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Koh, Eun-Hee (Department of Internal Medicine and Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Kim, Hyoun-Sik (Department of Internal Medicine and Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Lee, Jong-Hwi (Department of Chemical Engineering and Materials Science, Chung-Ang University)
  • 최혜민 (중앙대학교 화학신소재공학부) ;
  • 박철호 (중앙대학교 화학신소재공학부) ;
  • 이기업 (울산대학교 의과대학 아산생명과학연구소 내분비과) ;
  • 박중열 (울산대학교 의과대학 아산생명과학연구소 내분비과) ;
  • 고은희 (울산대학교 의과대학 아산생명과학연구소 내분비과) ;
  • 김현식 (울산대학교 의과대학 아산생명과학연구소 내분비과) ;
  • 이종휘 (중앙대학교 화학신소재공학부)
  • Published : 2007.12.21
Download PDF
⟨ Previous Next ⟩

Abstract

For decades, the various virtues of ${\alpha}-lipoic$ acid (ALA), a natural material synthesized in most cells, have been intensively studied and proved. Recently it was reported that ALA caused significant bodyweight reduction via appetite suppression. Unfortunately, the efficacy requires an administration over 50 mg/kg. The low bioavailability and the short plasma half life of ALA lead us to explore novel pharmaceutical dosage forms using nanoparticles. In this study, the effect of polymeric stabilizers on the bioavailability improvement of ALA nanoparticles was investigated. The reduction of particle size via nano-comminution technology was successful resulting in volume average particle sizes of 320 - 340 nm. The in vitro release rate of ALA did not reflect the decrease of particle size, possibly because of the self polymerization of ALA during nano-comminution. The type of polymeric stabilizers could not affect the release rate either. However, the in vivo food intake results of ALA showed that nano-suspensions were more effective than microparticles or a salt form. The nano-suspension containing polyvinyl pyrrolidone as the primary stabilizer and polyacrylic acid as the secondary stabilizer showed more improved efficacy for 2 hours.

Keywords

References

  1. R. M. Cicchillo and S. J. Booker, Mechanistric investigations of lipoic acid biosynthesis in escherichia coli: Both sulfur atoms in lipoic acid are contributied by the same lipoyl synthease polypeptide, J. Am. Chem. Soc., 127, 2860-2861 (2005) https://doi.org/10.1021/ja042428u
  2. D. Strodter, E. Lehmann, U. Lehmann, H. J. Trischler, R. G. Bretzel and K. Federlin, The influence of thioc acid on metabolism and function of the diabetic heart, Diabetes Res. Clin. Pract., 29, 19-26 (1995) https://doi.org/10.1016/0168-8227(95)01118-W
  3. L. Parker, H. J. Tritschler and K. Wessel, Neuroportection by the metabolic antioxidant alpha-lipoic acid, Free Radical Biol. Med, 22, 359-378 (1997) https://doi.org/10.1016/S0891-5849(96)00269-9
  4. M. K. Offermann and R. M. Medfod, Antioxidants and atherolsclerosis: A molecular perpective, Heart Dis. Stroke et al., 3, 52-57 (1994)
  5. B. Anna and W. Lidia, Lipoic acid-the drug of the future? Pharmacological Reports, 57, 570-577 (2005)
  6. W. J. Lee, I. K. Lee, H. S. Kim, Y. M. Kim, E. H. Koh, J. C. Won, S. M. Han, M.-S. Kim, I. Jo, G. T. Oh, I.-S. Park, J. H. Youn, S.-W. Park, K.-U. Lee, J.-Y. Park, Alpha-Lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase, Arterioscler Thromb. Vase. Biol., 25, 2488-2494 (2005) https://doi.org/10.1161/01.ATV.0000190667.33224.4c
  7. M. S. Kim, J. Y. Park, C. Namkoong, P. G. Jang, J. W. Ryu, H. S. Song, J. Y. Yun, I. S. Namgung, J. H. Ha, I. S. Park, I. K. Lee, V. Benoit, J. H. Youn, H. K. Lee and K. U. Lee, Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamin AMP-activated protein kinase, Nature Medicine, 10(7), 727-733 (2004) https://doi.org/10.1038/nm1061
  8. K. Marangon, S. Devaraj, O. Tirosh, L. Packer and I. Jialal, Comparison of the effect of alpha-lipoic acid and alphatocopherol supplementation on measures of oxidative stress, Free. Rad Biol. Med, 27, 1114 (1999) https://doi.org/10.1016/S0891-5849(99)00155-0
  9. D. H. Kim, H. J. Park, S. H. Kang, S. W. Jun, M.-S. Kim, S. Lee, J.-S. Park, S. J. Hwang, Preparation and characterization of lysozyme nanoparticles using solution enhanced dispersion by supercritical fluid (SEDS) process, J. Kor. Pharm. Sci., 35(2), 89-94 (2005)
  10. S. H. Park, J. H. Ahn, K. K. Moon, D. H. Bae, M.-S. Kim, S. Lee, T. W. Lee, J.-S. Woo, S.-J. Hwang, Study on the in vitro sun protection factor effect of nanosuspensions prepared using bead mill and high pressure homogenizer, J. Kor. Pharm. Sci., 35(6) 411-416 (2005)
  11. N. Rasenack and B. W. Muller, Micron-size drug particles: Common and novel micronization techniques, Pharm. Dev. Technol., 9, 1-13 (2004) https://doi.org/10.1081/PDT-120027417
  12. A. A. Noyes and W. R. Whitney, The rate of solution of solid substance in their own solutions, J. Am. Chem. Soc., 19, 930-934 (1897) https://doi.org/10.1021/ja02086a003
  13. G. G. Liversidge and K. C. Cundy, Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs, Int. J. Pharm., 125, 91-97 (1995) https://doi.org/10.1016/0378-5173(95)00122-Y
  14. E. Merisko-Liversidge, G. G. Liversidge and E. R. Cooper, Nanosizing: A formulation approach for poorly-water-soluble compounds, Eur. J. Pharm. Sci., 18, 113-120 (2003) https://doi.org/10.1016/S0928-0987(02)00251-8
  15. Y. Wu, A. Loper, E. Landis, L. Hettrick, L. Novak, K. Lynn, C. Chen, K. Thompson, R. Higgins, U. Batra, S. Shelukar, G. Kwei and D. Storey, The role of biopharmaceutics in the development of a clinical nanoparticle formulation of MK0869: A beagle dog model predicts improved bioavailability and diminished food effect on absorption in human, Int. J. Pharm., 285, 135-146 (2004) https://doi.org/10.1016/j.ijpharm.2004.08.001
  16. A. K. Andrianov and L. G. Payne, Polymeric carriers for oral uptake of microparticulates, Adv. Drug Deliv. Rev., 34, 155-170 (1998) https://doi.org/10.1016/S0169-409X(98)00038-6
  17. Y. Machida and T. Nagai, Directly compressed tablets containing hydroxypropyl cellulose in addition to starch or lactose, Chem. Pharm. Bull., 22, 2346-2351 (1974) https://doi.org/10.1248/cpb.22.2346
  18. G. W. Skinner, W. W. Harcum, P. E. Barnum and J. H. Guo, The evaluation of fme-particle hydroxypropylcellulose as a roller compaction binder in pharmaceutical applications, Drug Dev. Ind Pharm., 25, 1121-1128 (1999) https://doi.org/10.1081/DDC-100102278
  19. Anon, Final report on the safety assessment of hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropyl methylcellulose and cellulose gum, J. Am. Coll. Toxicol., 5, 1-60 (1986) https://doi.org/10.3109/10915818609140731
  20. J. D. R. Schulze, E. E. Peters, A. W. Vickers, J. S. Staton, M. D. Coffinb, G. E. Parsons, and A. W. Basit, Excipient effects on gastrointestinal transit and drug absorption in beagle dogs, Int. J. Pharm., 300, 67-75 (2005) https://doi.org/10.1016/j.ijpharm.2005.05.004
  21. V. Majerik, G. Charbit, E. Badens, G. Horvath, L. Szokonya, N. Bose and E. Teillaud, Bioavailability enhancement of an active substance by supercritical antisolvent precipitation, J. of Supercritical Fluids, 40, 101-110 (2007) https://doi.org/10.1016/j.supflu.2006.03.027
  22. A. V. Kabanov, E. V. Batrakova and V. Y. Alakhov, $Pluronic^{\circledR}$ block copolymers as novel polymer therapeutics for drug and gene delivery, J. Control. Release., 82, 189-212 (2002) https://doi.org/10.1016/S0168-3659(02)00009-3
  23. R. Barreiro-Iglesias, C. Alvarez-Lorenzo and A. Concheiro, Controlled release of estradiol solubilized in carbopol/surfactant aggregates, J. Control. Release, 93, 321-332 (2003)
  24. R. Barreiro-Iglesias, L. Bromberg, M. Temchenko, T. A. Hatton, C. Alvarez-Lorenzo and A. Concheiro, Solubilization and stabilization of camptothecin in micellar solutions of pluronic-g-poly(acrylic acid) copolymers, J. Control. Release, 97, 537-549 (2004) https://doi.org/10.1016/j.jconrel.2004.04.007
  25. P. Alexandridis, J. F. Holzwarth and T. A. Hatton, Micellization of poly( ethyleneoxide)-poly(propylene oxide)-poly (ethylene oxide) triblock copolymers in aqueous solutions:Thermodynamics of copolymer association, Macromolecules, 27, 2414-2425 (1994) https://doi.org/10.1021/ma00087a009
  26. M. Dittgen, M. Durrani and K. Lehmann, Acrylic polymers: A review of pharmaceutical applications, S.T.P. Pharma Sci., 7, 403-437 (1997)
  27. B. Perez-Marcos, C. Gutierrez, J. L. Gomez-Amoza, R. Martinez-Pacheco, C. Souto and A. Concheiro, Usefulness of certain varieties of carbomer in the formulation of hydrophilic furosemide matrices, Int. J. Pharm., 67, 113-121 (1991) https://doi.org/10.1016/0378-5173(91)90423-L
  28. J. Parojcic, Z. Ethuric, M. Jovanovic, S. Ibric and D. Jovanovic, Influence of dissolution media composition on drug release and in-vitro/in-vivo correlation for paracetamol matrix tablets prepared with novel carbomer polymers, J. Pharm. Pharmacol., 56, 735-741 (2004) https://doi.org/10.1211/0022357023583
  29. M. Paulsson and K. Edsman, Controlled drug release from gels using surfactant aggregates: I. Effect of lipophilic interactions for a series of uncharged substances, J. Pharm. Sci., 90, 1216-1225 (2001) https://doi.org/10.1002/jps.1075
  30. C. Alvarez-Lorenzo, J. L. Gomez-Amoza, R. MartinezPacheco, C. Souto and A. Concheiro, Evaluation of lowsubstituted hydroxypropyIcelluloses(L-HPCs) as filler-binders for direct compression, Int. J. Pharm., 197, 107-116 (2000) https://doi.org/10.1016/S0378-5173(99)00456-1