Olive-oil nanocapsules stabilized by HSA: influence of processing variables on particle properties

  • J. A. Molina-Bolívar
  • F. Galisteo-González
Research Paper


Liquid lipid nanocapsules (LLN) are considered to be promising drug carriers in the medical field. The size and the surface charge of these nanocarriers are of major importance, affecting their bioavailability and the in vivo behaviour after intravenous injection. This research provides a comprehensive study on the preparation of olive-oil nanocapsules stabilized with a human serum albumin shell (HSA). LLN were prepared by modified solvent-displacement method. Numerous experimental variables were examined in order to characterize their impact on LLN size, distribution, and electrophoretic mobility. Physicochemical parameters of LLN were controlled by adjusting the nanodroplet stabilizing shell of adsorbed protein molecules, which was affected by the oil:HSA ratio, pH, and ionic strength of aqueous medium. The stronger the repulsion between adsorbed HSA molecules, the smaller and more monodisperse the particles proved. Other process parameters, including the ethanol:acetone ratio, organic:aqueous phase ratio, speed of organic-phase injection, and stirring rate were examined to achieve optimum preparation conditions. LLN produced by our standardized formulation were in the range of 170–175 nm with low polydispersity index (<0.1). Long-term colloidal stability of samples was evaluated after 6 months of storage. Efficient incorporation of curcumin, a model for a water-insoluble drug, into olive-oil nanocapsules was achieved (90 %). Encapsulation of curcumin into LLN had a stabilizing effect with respect to drug photodecomposition compared to that of the free molecule in solution.


Olive-oil nanocapsules Physicochemical parameters Curcumin Drug delivery 



We thank David Nesbitt for reviewing the English in the manuscript.


  1. Ansari MJ, Ahmad S, Kohli K, Ali J, Khar RK (2005) Stability-indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations. J Pharm Biomed Anal 39:132–138CrossRefGoogle Scholar
  2. Anton N, Benoit JP, Saulnier P (2008) Design and production of nanoparticles formulated from nano-emulsion templates–a review. J Control Release 128:185–199CrossRefGoogle Scholar
  3. Arbós P, Arangoa MA, Campanero MA, Irache JM (2002) Quantification of the bioadhesive properties of protein-coated PVM/MA nanoparticles. Int J Pharm 242:129–136CrossRefGoogle Scholar
  4. Arbós P, Campanero MA, Arangoa MA, Irache JM (2004) Nanoparticles wiht specific bioadhesive properties to circumvent the pre-systemic degradation of fluorinated pyrimidines. J Control Release 96:55–65CrossRefGoogle Scholar
  5. Camner P, Lundborg M, Lastbom L, Gerde P, Gross N, Jarstrand C (2002) Experimental and calculated parameters on particle phagocytosis by alveolar macrophages. J Appl Physiol 92:2608–2616CrossRefGoogle Scholar
  6. Daglar B, Ozgur E, Corman ME, Urzun L, Demirel GB (2014) Polymeric nanocarriers for expected nanomedicine: current challenges and future prospects. RCS Adv 4:48639–48659Google Scholar
  7. Desai MP, Labhasetwar V, Amidon GL, Levy RJ (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13:1838–1845CrossRefGoogle Scholar
  8. Duncan R (2004) Nanomedicines in action. Pharm J 273:485–488Google Scholar
  9. Fessi H, Puisieux F, Deissaguet JP, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:R1–R4CrossRefGoogle Scholar
  10. Fonseca C, Simoes S, Gaspar R (2002) Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release 83:273–286CrossRefGoogle Scholar
  11. Freitas C, Muller RM (1998) Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticles (SLN) dispersion. Int J Pharm 168:221–229CrossRefGoogle Scholar
  12. He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surfasse charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31:3657–3666CrossRefGoogle Scholar
  13. Kaminaga Y, Nagatsu A, Akiyama A, Sugimoto N, Yamasaki T, Maitani T, Mizukami H (2003) Production of unnatural glucosides of curcumin with drastically enhanced water solubility by cell suspension cultures of Catharanthus roseus. FEBS Lett 555:311–316CrossRefGoogle Scholar
  14. Khalid MN, Simard P, Hoarau D, Dragomir A, Leroux JC (2006) Long circulating poly(ethylene glycol)-decorated lipid nanocapsules deliver docetaxel to solid tumors. Pharm Res 23:752–758CrossRefGoogle Scholar
  15. Lili Z, Zeyou Q, Qiyu H, Ke Z, Xiaoyi S, Juan L, You-Mian L (2014) Imprinted-like biopolymeric micelles as eficiente nanovehicles for curcumin delivery. Colloids Surf B: Biointerfaces 123:15–22CrossRefGoogle Scholar
  16. Liu J, Lv S, Chen L, Song L, Guo S, Huang S (2013) Recent progress in studying curcumin and its nano-preparations for cancer therapy. Curr Pharm Des 19:1974–1993Google Scholar
  17. Lozano MV, Torrecilla D, Torres D, Vidal A, Dominguez F, Alonso MJ (2008) Highly eficiente system to deliver taxanes into tumor cells; docetaxel-loaded chitosan oligomer coloidal carriers. Biomacromolecules 9:2186–2193CrossRefGoogle Scholar
  18. Madureira AR, Campos DA, Fonte P, Nunes S, Reis F, Gomes AM, Sarmento B, Pintado MM (2015) Characterization of solid lipid nanoparticles produced with carnauba wax for rosmarinic acid oral delivery. RCS Adv 5:22665–22673Google Scholar
  19. Manoocheri S, Darvishi B, Kamalinia G, Amini M, Fallah M, Ostad SN, Atyabi F, Dinarvand R (2013) Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel. DARU J Pharm Sci 21:58–68CrossRefGoogle Scholar
  20. Mora-Huertas CE, Fessi H, Elaissari A (2010) Polymer-based nanocapsules for drug delivery. Int J Pharm 385:113–142CrossRefGoogle Scholar
  21. Murakami H, Kobayashi M, Takeuchi H, Kawashima Y (1999) Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. Int J Pharm 187:143–152CrossRefGoogle Scholar
  22. Murali MY, Brij GK, Meena J, Subhash CC (2010) Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. J Colloid Interf Sci 351:19–29CrossRefGoogle Scholar
  23. Nassar T, Rom A, Nyska A, Benita S (2009) Novel double coated nanocapsules for intestinal delivery and enhanced oral bioavailability of tacrolimus a P-gp substrate drug. J Control Release 133:77–84CrossRefGoogle Scholar
  24. Nayak AP, Tiyaboonchai W, Patankar S, Madhusudhan B, Souto EB (2010) Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment. Colloid Surf B 81:263–273CrossRefGoogle Scholar
  25. Ourique AF, Pohlmann AR, Guterres SS, Beck RCR (2008) Tretionoin-loaded nanocapsules: preparation, physicochemical characterization, and photostability study. Int J Pharm 352:1–4CrossRefGoogle Scholar
  26. Patel A, Hu Y, Tiwari JK, Velikov KP (2010) Sysnthesis and characterization of zein-curcumin coloidal particles. Soft Matter 6:6192–6199CrossRefGoogle Scholar
  27. Pohlmann AR, Weiss W, Mertins O, Pesce da Silveria N, Guterres SS (2002) Spray-dried indomethacin-loaded polyester nanocapsules and nanospheres: development, stability evaluation and nanostructure models. Eur J Pharm Sci 16:305–312CrossRefGoogle Scholar
  28. Prego C, Fabre M, Torres D, Alonso MJ (2006) Efficacy and mechanisms of action of chitosan nanocapsules for oral peptide delivery. Pharm Res 23:549–556CrossRefGoogle Scholar
  29. Qiyu H, Lili Z, Xiaoyi S, Ke Z, Juan L, You-Nian L (2014) Coating of carboxymethyl dextran on liposomal curcumin to improve the anticancer activity. RCS Adv 4:59211–59217Google Scholar
  30. Quintanar D, Allémann E, Fessi H, Doelker E (1998a) Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm 24:1113–1128CrossRefGoogle Scholar
  31. Quintanar D, Allémann E, Doelker E, Fessi H (1998b) Preparation and characterization of nanocapsules from preformed polymers by a new process based on emulsification–diffusion technique. Pharm Res 15:1056–1062CrossRefGoogle Scholar
  32. Roger E, Lagarce F, Benoit J-P (2009) The gastrointestinal stability of lipid nanocapsules. Int J Pharm 379:260–265CrossRefGoogle Scholar
  33. Sahu A, Kasoju N, Bora U (2008) Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells. Biomacromolecules 9:2905–2912CrossRefGoogle Scholar
  34. Saracibar BL, Hermoso de Mendoza AE, Guada M, Vieitez CD, Prieto MJB (2012) Lipid nanoparticles for cancer therapy: state of the art and future prospects. Expert Opin Drug Deliv 9:1245–1261CrossRefGoogle Scholar
  35. Shaikh J, Ankola DD, Beniwal V, Singh D, Ravi Kumar MNV (2009) Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci 37:223–230CrossRefGoogle Scholar
  36. Song X, Zhao Y, Hou S, Xu F, Zhao R, He J, Cai Z, Li Y, Chen Q (2008) Dual agents loaded PLGA nanoparticles: systematic study of particle size and drug entrapment efficiency. Eur J Pharm Biopharm 69:445–453CrossRefGoogle Scholar
  37. Srivastava RM, Singh S, Dubey SK, Misra K, Khar A (2011) Immunomodulatory and therapeutic activity of curcumin. Int Immunopharmacol 11:331–341CrossRefGoogle Scholar
  38. Thanki K, Gangwal RP, Sangamwar AT, Jain S (2013) Oral delivery of anticancer drugs: challenges and opportunities. J Control Release 170:15–40CrossRefGoogle Scholar
  39. Thiele L, Diederichs JE, Reszka R, Merkle HP, Walter E (2003) Competitive adsorption of serum proteins at microparticles affects phagocytosis by dentritic cells. Biomaterial 24:1409–1418CrossRefGoogle Scholar
  40. Tonnesen HH, Karlsen J, van Henegouwen GB (1986) Studies on curcumin and curcuminoids VIII. Photochemical stability of curcumin. Eur Food Res Technol 183:116–122Google Scholar
  41. Tsuyoshi H, Kenjiro O, Masahito Y (2010) Curcumin and Alzheimer´s Disease. CNS Neurosci Ther 16:285–297CrossRefGoogle Scholar
  42. Vauthier C, Bouchemal K (2009) Methods for the preparation and manufacture of polymeric nanoparticles. Pharm Res 26:1025–1058CrossRefGoogle Scholar
  43. Yuanm F, Leuning M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK (1994) Microvascular permeability and interstitial penetration of sterically stabilized (Stealth) liposomes in a human tumor xenograft. Cancer Res 54:3352–3356Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Department of Applied Physics II, Engineering SchoolUniversity of MálagaMálagaSpain
  2. 2.Department of Applied PhysicsUniversity of GranadaGranadaSpain

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