AAPS PharmSciTech

, Volume 18, Issue 4, pp 1261–1269 | Cite as

Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds

  • Baptiste Martin
  • Fabien Brouillet
  • Sophie Franceschi
  • Emile Perez
Research Article

Abstract

The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.

Keywords

Drug delivery Indomethacin Ketoconazole Organogel nanoparticles 12-hydroxystearic acid 

References

  1. 1.
    Bunjes H. Lipid nanoparticles for the delivery of poorly water-soluble drugs: lipid nanoparticles. J Pharm Pharmacol. 2010;62(11):1637–45.CrossRefPubMedGoogle Scholar
  2. 2.
    Das S, Ng WK, Tan RBH. Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? Eur J Pharm Sci. 2012;47(1):139–51.CrossRefPubMedGoogle Scholar
  3. 3.
    Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366(1–2):170–84.CrossRefPubMedGoogle Scholar
  4. 4.
    Khandavilli S, Panchagnula R. Nanoemulsions as versatile formulations for paclitaxel delivery: peroral and dermal delivery studies in rats. J Invest Dermatol. 2007;127(1):154–62.CrossRefPubMedGoogle Scholar
  5. 5.
    Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH. Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm. 2011;414(1–2):267–75.CrossRefPubMedGoogle Scholar
  6. 6.
    Tiwari R, Pathak K. Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: comparative analysis of characteristics, pharmacokinetics and tissue uptake. Int J Pharm. 2011;415(1–2):232–43.CrossRefPubMedGoogle Scholar
  7. 7.
    Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano-emulsions. Adv Colloid Interface Sci. 2004;108–109:303–18.CrossRefPubMedGoogle Scholar
  8. 8.
    Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54:S131–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Freitas C, Müller RH. Correlation between long-term stability of solid lipid nanoparticles (SLNTM) and crystallinity of the lipid phase. Eur J Pharm Biopharm. 1999;47(2):125–32.CrossRefPubMedGoogle Scholar
  10. 10.
    Anand B, Pisal SS, Paradkar AR, Mahadik KR. Applications of organogels in pharmaceuticals. J Sci Ind Res. 2001;60:311–8.Google Scholar
  11. 11.
    Vintiloiu A, Leroux J-C. Organogels and their use in drug delivery—a review. J Control Release. 2008;125(3):179–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Debnath S, Vanitha G, Bindu HP, Babu NM. Applications of organogels in drug delivery. Indian J Res Pharm Biotechnol. 2014;2(1):976.Google Scholar
  13. 13.
    Motulsky A, Lafleur M, Couffin-Hoarau A-C, Hoarau D, Boury F, Benoit J-P, et al. Characterization and biocompatibility of organogels based on l-alanine for parenteral drug delivery implants. Biomaterials. 2005;26(31):6242–53.CrossRefPubMedGoogle Scholar
  14. 14.
    Iwanaga K, Sumizawa T, Miyazaki M, Kakemi M. Characterization of organogel as a novel oral controlled release formulation for lipophilic compounds. Int J Pharm. 2010;388(1–2):123–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Bhatia A, Singh B, Raza K, Wadhwa S, Katare OP. Tamoxifen-loaded lecithin organogel (LO) for topical application: development, optimization and characterization. Int J Pharm. 2013;444(1–2):47–59.CrossRefPubMedGoogle Scholar
  16. 16.
    Pereira Camelo SR, Franceschi S, Perez E, Girod Fullana S, Ré MI. Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug. Drug Dev Ind Pharm. 2015;7:1–13.Google Scholar
  17. 17.
    Kirilov P, Lukyanova L, Franceschi-Messant S, Perier V, Perez E, Rico-Lattes I. A new type of colloidal dispersions based on nanoparticles of gelled oil. Colloids Surf Physicochem Eng Asp. 2008;328(1–3):1–7.CrossRefGoogle Scholar
  18. 18.
    Kirilov P, Gauffre F, Franceschi-Messant S, Perez E, Rico-Lattes I. Rheological characterization of a new type of colloidal dispersion based on nanoparticles of gelled oil. J Phys Chem B. 2009;113(32):11101–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Kirilov P, Rum S, Gilbert E, Roussel L, Salmon D, Abdayem R, et al. Aqueous dispersions of organogel nanoparticles—potential systems for cosmetic and dermo-cosmetic applications. Int J Cosmet Sci. 2014;36(4):336–46.CrossRefPubMedGoogle Scholar
  20. 20.
    Boudier A, Kirilov P, Franceschi-Messant S, Haouaria B, Hadioui L, Roques R, et al. Evaluation of biocompatible stabilised gelled soya bean oil nanoparticles as new hydrophobic reservoirs. J Microencapsul. 2010;27(8):682–92.CrossRefPubMedGoogle Scholar
  21. 21.
    Siqueira-Moura MP, Franceschi-Messant S, Blanzat M, Ré MI, Perez E, Rico-Lattes I, et al. Gelled oil particles: a new approach to encapsulate a hydrophobic metallophthalocyanine. J Colloid Interface Sci. 2013;401:155–60.CrossRefPubMedGoogle Scholar
  22. 22.
    Yu H, Huang Q. Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions. J Agric Food Chem. 2012;60(21):5373–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Varshosaz J, Andalib S, Tabbakhian M, Ebrahimzadeh N. Development of lecithin nanoemulsion based organogels for permeation enhancement of metoprolol through rat skin. J Nanomater. 2013;2013:1–10.Google Scholar
  24. 24.
    Bei W, Zhou Y, Xing X, Zahi MR, Li Y, Yuan Q, et al. Organogel-nanoemulsion containing nisin and D-limonene and its antimicrobial activity. Front Microbiol [Internet]. 2015 Sep 22 [cited 2016 May 20];6. Available from: http://journal.frontiersin.org/Article/10.3389/fmicb.2015.01010/abstract
  25. 25.
    Ricci M, Puglia C, Bonina F, Giovanni CD, Giovagnoli S, Rossi C. Evaluation of indomethacin percutaneous absorption from nanostructured lipid carriers (NLC): in vitro and in vivo studies. J Pharm Sci. 2005;94(5):1149–59.CrossRefPubMedGoogle Scholar
  26. 26.
    Shakeel F, Ramadan W, Gargum HM, Singh R. Preparation and in vivo evaluation of indomethacin loaded true nanoemulsions. Sci Pharm. 2010;78(1):47–56.CrossRefPubMedGoogle Scholar
  27. 27.
    Souto EB, Müller RH. SLN and NLC for topical delivery of ketoconazole. J Microencapsul. 2005;22(5):501–10.CrossRefPubMedGoogle Scholar
  28. 28.
    Clarysse S, Psachoulias D, Brouwers J, Tack J, Annaert P, Duchateau G, et al. Postprandial changes in solubilizing capacity of human intestinal fluids for BCS class II drugs. Pharm Res. 2009;26(6):1456–66.CrossRefPubMedGoogle Scholar
  29. 29.
    Ould-Ouali L, Ariën A, Rosenblatt J, Nathan A, Twaddle P, Matalenas T, et al. Biodegradable self-assembling PEG-copolymer as vehicle for poorly water-soluble drugs. Pharm Res. 2004;21(9):1581–90.CrossRefPubMedGoogle Scholar
  30. 30.
    Mhaske RA. Identification of major degradation products of ketoconazole. Sci Pharm. 2011;79(4):817–36.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tita B, Fulias A, Tita D. Kinetic study of indomethacin under isothermal conditions. Rev Chim Bucuresti. 2010;61:1037–41.Google Scholar
  32. 32.
    Kim N, Sudol ED, Dimonie VL, El-Aasser MS. Poly(vinyl alcohol) stabilization of acrylic emulsion polymers using the miniemulsion approach. Macromolecules. 2003;36(15):5573–9.CrossRefGoogle Scholar
  33. 33.
    Delmas T, Piraux H, Couffin A-C, Texier I, Vinet F, Poulin P, et al. How to prepare and stabilize very small nanoemulsions. Langmuir. 2011;27(5):1683–92.CrossRefPubMedGoogle Scholar
  34. 34.
    Hippalgaonkar K, Adelli GR, Hippalgaonkar K, Repka MA, Majumdar S. Indomethacin-loaded solid lipid nanoparticles for ocular delivery: development, characterization, and in vitro evaluation. J Ocul Pharmacol Ther. 2013;29(2):216–28.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Muchtar S, Abdulrazik M, Frucht-Pery J, Benita S. Ex-vivo permeation study of indomethacin from a submicron emulsion through albino rabbit cornea. J Control Release. 1997;44(1):55–64.CrossRefGoogle Scholar
  36. 36.
    Saarinen-Savolainen P, Järvinen T, Taipale H, Urtti A. Method for evaluating drug release from liposomes in sink conditions. Int J Pharm. 1997;159(1):27–33.CrossRefGoogle Scholar
  37. 37.
    Chen H, Khemtong C, Yang X, Chang X, Gao J. Nanonization strategies for poorly water-soluble drugs. Drug Discov Today. 2011;16(7–8):354–60.CrossRefPubMedGoogle Scholar
  38. 38.
    Van Hoogevest P, Liu X, Fahr A. Drug delivery strategies for poorly water-soluble drugs: the industrial perspective. Expert Opin Drug Deliv. 2011;8(11):1481–500.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • Baptiste Martin
    • 1
  • Fabien Brouillet
    • 2
  • Sophie Franceschi
    • 1
  • Emile Perez
    • 1
  1. 1.Laboratoire des IMRCPUniversité de Toulouse, CNRS UMR 5623, UPSToulouseFrance
  2. 2.Faculté de PharmacieCIRIMAT, Université de Toulouse, CNRS, INPT, UPSToulouse Cedex 9France

Personalised recommendations