Preparation of Resveratrol-loaded Poly($\varepsilon$-caprolactone) Nanoparticles by Oil-in-water Emulsion Solvent Evaporation Method

  • Published : 2009.02.28

Abstract

Resveratrol-loaded poly($\varepsilon$-caprolactone) (PCL) nanoparticles were prepared by oil in water (O/W) emulsion solvent evaporation method. The morphology of the nanoparticles was evaluated using atomic force microscope (AFM), in which well-shaped and rigid nanoparticles were prepared. The mean particle size of nanoparticles prepared using only dichloromethane (DCM) ($523.5{\pm}36.7\;nm$) was larger than that prepared with a mixture of DCM and either ethanol (EtOH) ($494.5{\pm}29.2\;nm$) or acetone ($493.5{\pm}6.9\;nm$). The encapsulation efficiency of nanoparticles prepared only with DCM as dispersed phase ($78.3{\pm}7.7%$) was the highest of those prepared with solvent mixtures. An increase in the molecular weight of PCL led to an increase in encapsulation efficiency (from $78.3{\pm}7.7$ to $91.4{\pm}3.2%$). Pluronic F-127 produced the smallest mean size ($523.5{\pm}36.7\;nm$) with the narrowest particle size distribution. These results show that dispersed phase, molecular weight of wall materials, emulsion stabilizer could be important factors to affect the properties of nanoparticles.

Keywords

References

  1. Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (pLGA) devices. Biomaterials 21: 2475-2490 (2000) https://doi.org/10.1016/S0142-9612(00)00115-0
  2. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticies as drug devices. J. Control. Release 20: 1-20 (2001) https://doi.org/10.1016/S0168-3659(00)00339-4
  3. Yin J, Noda Y, Yotsuyanagi T. Properties of poly(lactide-co-glycolic acid) nanospheres containing protease inhibitors: Camostat mesilate B. and nafamostat mesilate. Int. J. Pharm. 314: 46-55 (2006) https://doi.org/10.1016/j.ijpharm.2006.01.047
  4. Chen L, Remondetto GE, Subirade M. Food protein-based materials as nutraceutical delivery systems. Trends Food Sci. Tech. 17: 272-283 (2006) https://doi.org/10.1016/j.tifs.2005.12.011
  5. Verger ML, Fluckiger L, Kim Yl, Hoffman M, Maincent P. Preparation and characterization of nanoparticies containing and antihypertensive agent. Eur. J. Pharm. Biopharm. 46: 137-143 (1998) https://doi.org/10.1016/S0939-6411(98)00015-0
  6. Perez MH, Zinutti C, Lamprecht A, Ubrich N, Astier A, Hoffman M, Bodmeier R, Maincent P. The preparation and evaluation of poly($\varepsilon$-caprolactone) microparticies containing both a lipophilic and a hydrophilic drug. J. Control. Release 65: 429-438 (2000) https://doi.org/10.1016/S0168-3659(99)00253-9
  7. Jiao YY, Ubrich N, Hoffart V, Marchand-Arvier M, Vigneron C, Hoffman M, Maincent P. Preparation and characterization of heparin-loaded polymeric microparticies. Drug Dev. Ind. Pharm. 28:1033-1041 (2002) https://doi.org/10.1081/DDC-120014740
  8. Kim BK, Hwang SJ, Park ill, Park HJ. Characteristics of felodipine-located poly($\varepsilon$-caprolactone) microspheres. J. Microencapsul. 22: 193-203 (2005) https://doi.org/10.1080/02652040400015346
  9. Benoit MA, Baras B, Gillard J. Preparation and characterization of protein-loaded poly($\varepsilon$-caprolactone) microparticies for oral vaccine delivery. Int. J. Pharm. 184: 73-84 (1999) https://doi.org/10.1016/S0378-5173(99)00109-X
  10. Yang YY, Chung TS, Ng NP. Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. Biomaterials 22: 231-241 (2001) https://doi.org/10.1016/S0142-9612(00)00178-2
  11. Chen DR, Bei JZ, Wang SG. Polycaprolactone microparticles and their biodegradation. Polym. Degrad. Stabil. 66: 455-459 (2000) https://doi.org/10.1016/S0141-3910(99)00145-7
  12. Lamprecht A, Ubrich N, Perez MH, Lehr CM, Hoffman M, Maincent P. Influence of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique. Int. J. Pharm. 196: 177-182 (2000) https://doi.org/10.1016/S0378-5173(99)00422-6
  13. Barbato F, Rotonda MIL, Maglio G, Palumbo R, Quaglia F. Biodegradable microspheres of novel segmented poly(ether-ester-amide)s based on poly($\varepsilon$-caprolactone) for the delivery of bioactive compounds. Biomaterials 22: 1371-1378 (2001) https://doi.org/10.1016/S0142-9612(00)00291-X
  14. looss P, Ray AML, Grimandi G, Daculsi G, Merle C. A new injectable bone substitute combining poly($\varepsilon$-caprolactone) microparticies with biphasic calcium phosphate granules. Biomaterials 22: 2785-2794 (2001) https://doi.org/10.1016/S0142-9612(01)00022-9
  15. Youan BBC, Jacson TL, Dickens L, Hernandez C, Ababio GO. Protein release profiles and morphology of biodegradable microcapsules containing an oily core. J. Control. Release 76: 313-326 (2001) https://doi.org/10.1016/S0168-3659(01)00445-X
  16. Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am. J. Enol. Viticult. 43: 49-52 (1992)
  17. Labinskyy N, Csiszar A, Veress G, Stef G, Pacher P, Oroszi G, Wu J, Ungvari Z. Vascular dysfunction in aging: Potential effects of resveratrol, an anti-inflammatory phytoestrogen. Curr. Med. Chem. 13: 989-996 (2006) https://doi.org/10.2174/092986706776360987
  18. Goldberg DM, Yan J, Soleas GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin. Biochem. 36: 79-87 (2003) https://doi.org/10.1016/S0009-9120(02)00397-1
  19. Zhao J, Liu CS, Yuan Y, Tao XY, Shan XQ, Sheng Y, Wu F. Preparation of hemoglobin-loaded nano-sized particies with porous structure as oxygen carriers. Biomaterials 28: 1414-1422 (2007) https://doi.org/10.1016/j.biomaterials.2006.10.012
  20. Viswanathan NB, Thomas PA, Pandit JK, Kulkarni MG, Mashelkar RA. Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique. J. Control. Release 58: 9-20 (1999) https://doi.org/10.1016/S0168-3659(98)00140-0
  21. Kim BK, Hwang SJ, Park JB, Park HJ. Preparation and characterization of drug-loaded polymethacrylate microspheres by an emulsion solvent evaporation method. J. Microencapsul. 19: 811-822 (2002) https://doi.org/10.1080/0265204021000022770
  22. Herrmann J, Bodmeier R. Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and nonaqueous solvent evaporation methods. Eur. J. Pharm. Biopharm. 45:75-82 (1998) https://doi.org/10.1016/S0939-6411(97)00125-2
  23. Kawashima Y, Yamamoto H, Takeuchi H, Hino T, Niwa T. Properties of a peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods. Eur. J. Pharm. Biopharm. 45: 41-48 (1998) https://doi.org/10.1016/S0939-6411(97)00121-5
  24. Lamosa MLL, Lopez CR, Jato JLV, Alonso MJ. Design of microencapsulated chitosan microspheres for colonic drug delivery. J. Control. Release 52: 109-118 (1998) https://doi.org/10.1016/S0168-3659(97)00203-4
  25. Rodriguez M, Jose LV, Torres D. Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region. J. Control. Release 55: 67-77 (1998) https://doi.org/10.1016/S0168-3659(98)00029-7
  26. Lee JH, Park TG, Choi HK. Effect of formulation and processing variables on the characteristics of microspheres for water soluble drugs prepared by w/o/o double emulsion solvent diffusion method. Int. J. Pharm. 196: 75-83 (2000) https://doi.org/10.1016/S0378-5173(99)00440-8
  27. Amorim MJLGB, Ferreira JPM. Microparticles for delivering therapeutic peptides and proteteins to the lumen of the small intestine. Eur. J. Pharm. Biopharm. 52: 39-44 (2001) https://doi.org/10.1016/S0939-6411(01)00148-5
  28. Sah H. Ethyl formate- alternative dispersed solvent useful in preparing PLGA microspheres. Int. J. Pharm. 195: 103-113 (2000) https://doi.org/10.1016/S0378-5173(99)00379-8
  29. Chernysheva YV, Babak VG, Kildeeva NR, Boury F, Benoit JP, Ubrich N, Maincent P. Effect of the type of hydrophobic polymers on the size of nanoparticles obtained by emulsification-solvent evaporation. Mendeleev Commun. 13: 65-67 (2003) https://doi.org/10.1070/MC2003v013n02ABEH001690