화학공학소재연구정보센터
Macromolecular Research, Vol.27, No.6, 579-585, June, 2019
Controlling the Release Profile Through Phase Control of Calcium Phosphate-Alginate Core-shell Nanoparticles in Gene Delivery
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In this study, we aimed to control the drug release rate from calcium phosphate-alginate (CaP-Alg) core-shell nanoparticle (NPs) using CaP phases (brushite (DCPD) [Bru] and hydroxyapatite [HA]) generated under different pH conditions. Core-shell NPs consisted of an inorganic CaP core and an organic Alg shell and were synthesized by the water-in-oil emulsification and precipitation method. CaP-Alg NPs were synthesized under different pH conditions, resulting in the mineralization of CaP with Bru and HA in the core region of core-shell NPs. Albumin-fluorescein isothiocyanate conjugate (FITC-BSA) was used as a model drug for in-vitro drug release studies. CaP-Alg (Bru-Alg and HA-Alg) NPs exhibited a higher loading capacity and encapsulation efficiency than Ca-Alg NPs. The release behavior of synthesized core-shell NPs showed different patterns due to the pH-sensitivity of Alg and CaP. At physiological pH, Ca-Alg NPs exhibited an initial burst release behavior, while CaP-Alg showed controlled release behavior. Our results demonstrate that HA-Alg NPs are more suitable for controlled intracellular delivery while Bru-Alg NPs are more suitable for extracellular compartment delivery. Therefore, CaP-Alg NPs could be potential candidates for controlled gene and biomolecule delivery into cells for therapeutic purposes.
  1. Mohtaram NK, Montgomery A, Willerth SM, Biomed. Mater., 8, 22001 (2013)
  2. Lee K, Silva EA, Mooney DJ, J. R. Soc. Interface, 8, 153 (2011)
  3. Huyer LD, Montgomery M, Zhao Y, Xiao Y, Conant G, Korolj A, Radisic M, Biomed. Mater., 10, 034004 (2015)
  4. Fang YL, Chen XG, Godbey WT, J. Biomed. Mater. Res. B, 103, 1679 (2015)
  5. Jebahi S, Oudadesse H, Saleh GB, Saoudi M, Mesadhi S, Rebai T, Keskes H, el Feki A, el Feki H, Korean J. Chem. Eng., 31(9), 1616 (2014)
  6. Park U, Kim K, Biotechnol. Bioproc. E., 22, 659 (2017)
  7. Tran M, Wang C, Front. Chem. Sci. Eng., 8, 225 (2014)
  8. Hollister SJ, Nat. Mater., 4, 518 (2005)
  9. Silva GA, Ducheyne P, Reis RL, J. Tissue Eng. Regen. Med., 1, 4 (2007)
  10. Wang AZ, Gu F, Zhang L, Chan JM, Radovic-Moreno A, Shaikh MR, Farokhzad OC, Expert Opin. Biol. Ther., 8, 1063 (2008)
  11. Zhang S, Uludag H, Pharm. Res., 26, 1561 (2009)
  12. Thomson RC, Wake MC, Yaszemski MJ, Mikos AG, in Biopolymers II, Springer Berlin Heidelberg, pp. 245-274.
  13. Lin CC, Metters AT, Adv. Drug Deliv. Rev., 58, 1379 (2006)
  14. Srouji S, Kizhner T, Suss-Tobi E, Livne E, Zussman E, J. Mater. Sci. -Mater. Med., 19, 1249 (2008)
  15. Ghosh K, Pan Z, Guan E, Ge S, Liu Y, Nakamura T, Ren XD, Rafailovich M, Clark RAF, Biomaterials, 28, 671 (2007)
  16. Jang J, Oh H, Lee J, Song TH, Jeong YH, Cho DW, Appl. Phys. Lett., 102, 211914 (2013)
  17. Suzuki S, Asoh TA, Kikuchi A, J. Biomed. Mater. Res. A, 101A, 1345 (2013)
  18. Mandal B, Bhattacharjee H, Mittal N, Sah H, Balabathula P, Thoma LA, Wood GC, Nanomed. Nanotechnol. Biol. Med., 9, 474 (2013)
  19. Paradee N, Sirivat A, Niamlang S, Prissanaroon-Ouajai W, J. Mater. Sci. -Mater. Med., 23, 999 (2012)
  20. Zhao XL, Ding XB, Deng ZH, Zheng ZH, Peng YX, Long XP, Macromol. Rapid Commun., 26(22), 1784 (2005)
  21. Dumitrescu AM, Slatineanu T, Poiata A, Iordan AR, Mihailescu C, Palamaru MN, Colloids Surf. A: Physicochem. Eng. Asp., 455, 185 (2014)
  22. Lee D, Upadhye K, Kumta PN, Mater. Sci. Eng. B-Solid State Mater. Adv. Technol., 177, 289 (2012)
  23. Mostaghaci B, Loretz B, Lehr CM, Curr. Pharm. Des., 22, 1529 (2016)
  24. Xie Y, Chen Y, Sun M, Ping Q, Curr. Pharm. Biotechnol., 14, 918 (2013)
  25. Olton D, Li J, Wilson ME, Rogers T, Close J, Huang L, Kumta PN, Sfeir C, Biomaterials, 28, 1267 (2007)
  26. Chen SH, Chen CH, Shalumon KT, Chen JP, Int. J. Nanomedicine, 9, 4079 (2014)
  27. Ahn SJ, Shin YM, Kim SE, Jeong SI, Jeong JO, Park JS, et al., Biotechnol. Bioproc. E., 20, 948 (2015)
  28. Amini Y, Moradi B, Tafaghodi M, Meshkat Z, Ghazvini K, Fasihi-Ramandi M, Biotechnol. Bioproc. E., 21, 653 (2016)
  29. Shin YM, Park JS, Jeong SI, An SJ, Gwon HJ, Lim YM, Nho YC, Kim CY, Biotechnol. Bioproc. E., 19, 341 (2014)
  30. Ciobanu G, Harja M, Rusu L, Mocanu AM, Luca C, Korean J. Chem. Eng., 31(6), 1021 (2014)
  31. Huang S, Fu X, J. Control. Release, 142, 149 (2010)
  32. Uskokovic V, Desai TA, J. Biomed. Mater. Res. A, 101A, 1427 (2013)
  33. Yang J, Chen J, Pan D, Wan Y, Wang Z, Carbohydr. Polym., 92, 719 (2013)
  34. Leveque I, Rhodes KH, Mann S, J. Mater. Chem., 12, 2178 (2002)
  35. Liang YH, Liu CH, Liao SH, Lin YY, Tang HW, Liu SY, Lai IR, Wu KCW, ACS Appl. Mater. Interfaces, 4, 6720 (2012)
  36. Xie J, Riley C, Kumar M, Chittur K, Biomaterials, 23, 3609 (2002)
  37. Lee MS, Lee JE, Byun E, Kim NW, Lee K, Lee H, Sim SJ, Lee DS, Jeong JH, J. Control. Release, 192, 122 (2014)
  38. Uskokovic V, Uskokovic DP, J. Biomed. Mater. Res. B, 96, 152 (2011)