Skip to main content
SpringerLink
Log in

Synthesis and evaluation of hydroponically alginate nanoparticles as novel carrier for intravenous delivery of propofol

  • Delivery Systems
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Commercial lipid emulsion of propofol (CLE) has several drawbacks including pain on injection and emulsion instability. In this paper, a novel nanocarrier system is introduced to improve stability and solubility of the poorly soluble anesthetic drug, propofol, for intravenous administration. In this paper, alginate is modified using a facile method in which the carboxylic group of alginate is grafted to octanol. The octanol–grafted alginate (Alg–C8) is then employed to prepare nanoparticles which are subsequently used for encapsulation of propofol. The nanoparticles are analyzed for their pH, osmolarity, particle size, stability, morphology and sleep recovery and the results are compared with CLE as control. It is revealed that nanoparticles have the average particle size of 180 nm ± 1.2 and spherical morphology which is less than CLE while their pH, osmolarity and profile of release of formulated nanoparticles are similar to those of CLE. In addition, the results show good chemical and physical storage stability for the nanoparticles at room temperature for at least 6 months compared to CLE as control. The animal sleep recovery test on rats shows no significant difference in time of unconsciousness and recovery of the righting reflex between nanoparticles and CLE. It is concluded that encapsulated nanoparticles introduced here could be a promising clinical intravenous system for delivery of poorly soluble anesthetic propofol. In addition, this study provides an efficient and facile method for preparing a carrier system for water insoluble drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Miner JR, Burton JH. Clinical practice advisory: emergency department procedural sedation with propofol. Ann Emerg Med. 2007;50(2):182. e1–187. e1.

    Article  Google Scholar 

  2. Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation two randomized controlled trials. J Am Med Assoc. 2012;307(11):1151–60.

    Article  Google Scholar 

  3. Langley MS, Heel RC. Propofol Drugs. 1988;35(4):334–72.

    Article  Google Scholar 

  4. Brambrink AM, Dissen GA, Martin LD, Creeley CE, Olney JW. Propofol-induced apoptosis of neurons and oligodendrocytes in neonatal macaque brain. In: Proceedings of the American Society of Anesthesiologists, Washington, DC; 2012. p. 13–17.

  5. Sundarathiti P, Boonthom N, Chalacheewa T, Jommaroeng P, Rungsithiwan W. A comparison of propofol-LCT with propofol-LCT/MCT on pain of injection. Med J Med Assoc Thail. 2007;90(12):2683.

    Google Scholar 

  6. Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet. 2001;357(9256):606–7.

    Article  Google Scholar 

  7. Lee T, Loewenthal A, Strachan J, Todd B. Pain during injection of propofol. Anaesthesia. 1994;49(9):817–8.

    Article  Google Scholar 

  8. Wachowski I, Jolly DT, Hrazdil J, Galbraith JC, Greacen M, Clanachan AS. The growth of microorganisms in propofol and mixtures of propofol and lidocaine. Anesth Analg. 1999;88(1):209–12.

    Google Scholar 

  9. Jung J, Choi B, Cho S, Choe S, Ghim J, Lee H, et al. Effectiveness, safety, and pharmacokinetic and pharmacodynamic characteristics of microemulsion propofol in patients undergoing elective surgery under total intravenous anaesthesia. Br J Anaesth. 2010;104(5):563–76.

    Article  Google Scholar 

  10. Morey TE, Modell JH, Shekhawat D, Shah DO, Klatt B, Thomas GP, et al. Anesthetic properties of a propofol microemulsion in dogs. Anesth Analg. 2006;103(4):882–7.

    Article  Google Scholar 

  11. Kim K-M, Choi B-M, Park S-W, Lee S-H, Christensen LV, Zhou J, et al. Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion. Anesthesiology. 2007;106(5):924–34.

    Article  Google Scholar 

  12. Pergolizzi JV, Gan TJ, Plavin S, Labhsetwar S, Taylor R. Perspectives on the role of fospropofol in the monitored anesthesia care setting. Anesthesiol Res Pract. 2011;2011:458920. doi:10.1155/2011/458920.

    Google Scholar 

  13. Silvestri GA, Vincent BD, Wahidi MM, Robinette E, Hansbrough JR, Downie GH. A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy. CHEST J. 2009;135(1):41–7.

    Article  Google Scholar 

  14. Trapani A, Laquintana V, Lopedota A, Franco M, Latrofa A, Talani G, et al. Evaluation of new propofol aqueous solutions for intravenous anesthesia. Int J Pharm. 2004;278(1):91–8.

    Article  Google Scholar 

  15. Ravenelle F, Gori S, Le Garrec D, Lessard D, Luo L, Palusova D, et al. Novel lipid and preservative-free propofol formulation: properties and pharmacodynamics. Pharm Res. 2008;25(2):313–9.

    Article  Google Scholar 

  16. Ravenelle F, Vachon P, Rigby-Jones A, Sneyd J, Le Garrec D, Gori S, et al. Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation. Br J Anaesth. 2008;101(2):186–93.

    Article  Google Scholar 

  17. Zhou Y, Yang J, Liu J, Wang Y, Zhang W. Efficacy comparison of the novel water-soluble propofol prodrug HX0969w and fospropofol in mice and rats. Br J Anaesth. 2013;111(5):825–32.

    Article  Google Scholar 

  18. Cohen L. Clinical trial: a dose–response study of fospropofol disodium for moderate sedation during colonoscopy. Aliment Pharmacol Ther. 2008;27(7):597–608.

    Article  Google Scholar 

  19. Egan TD, Kern SE, Johnson KB, Pace NL. The pharmacokinetics and pharmacodynamics of propofol in a modified cyclodextrin formulation (Captisol®) versus propofol in a lipid formulation (Diprivan®): an electroencephalographic and hemodynamic study in a porcine model. Anesth Analg. 2003;97(1):72–9.

    Article  Google Scholar 

  20. Trapani G, Latrofa A, Franco M, Lopedota A, Sanna E, Liso G. Inclusion complexation of propofol with 2-hydroxypropyl-β-cyclodextrin. Physicochemical, nuclear magnetic resonance spectroscopic studies, and anesthetic properties in rat. J Pharm Sci. 1998;87(4):514–8.

    Article  Google Scholar 

  21. Han YK, Jeong CW, Lee HG. Pain reduction on injection of microemulsion propofol via combination of remifentanil and lidocaine. Korean J Anesthesiol. 2010;58(5):435–9.

    Article  Google Scholar 

  22. Sim JY, Lee SH, Park DY, Jung JA, Ki KH, Lee DH, et al. Pain on injection with microemulsion propofol. Br J Clin Pharmacol. 2009;67(3):316–25.

    Article  Google Scholar 

  23. Ohmizo H, Obara S, Iwama H. Mechanism of injection pain with long and longmedium chain triglyceride emulsive propofol. Can J Anaesth. 2005;52(6):595–9.

    Article  Google Scholar 

  24. Barreiro-Iglesias R, Bromberg L, Temchenko M, Hatton TA, Concheiro A, Alvarez-Lorenzo C. Solubilization and stabilization of camptothecin in micellar solutions of pluronic- < i > g </i > -poly (acrylic acid) copolymers. J Control Rel. 2004;97(3):537–49.

    Article  Google Scholar 

  25. Wilhelm M, Zhao CL, Wang Y, Xu R, Winnik MA, Mura JL, et al. Poly (styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study. Macromolecules. 1991;24(5):1033–40.

    Article  Google Scholar 

  26. Li C, Zhang Y, Hu J, Cheng J, Liu S. reversible three-state switching of multicolor fluorescence emission by multiple stimuli modulated FRET processes within thermoresponsive polymeric micelles. Angew Chem. 2010;122(30):5246–50.

    Article  Google Scholar 

  27. Wei Z, Hao J, Yuan S, Li Y, Juan W, Sha X, et al. Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization. Int J Pharm. 2009;376(1):176–85.

    Article  Google Scholar 

  28. Aydelotte MB, Thonar EJ, Mollenhauer J, Flechtenmacher J. Culture of chondrocytes in alginate gel: variations in conditions of gelation influence the structure of the alginate gel, and the arrangement and morphology of proliferating chondrocytes. In Vitro Cell Dev Biol-Animal. 1998;34(2):123–30.

    Article  Google Scholar 

  29. Cao Y, Rodriguez A, Vacanti M, Ibarra C, Arevalo C, Vacanti CA. Comparative study of the use of poly (glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage. J Biomater Sci Polym Ed. 1998;9(5):475–87.

    Article  Google Scholar 

  30. Tønnesen HH, Karlsen J. Alginate in drug delivery systems. Drug Dev Ind Pharm. 2002;28(6):621–30.

    Article  Google Scholar 

  31. Gombotz WR, Wee SF. Protein release from alginate matrices. Adv Drug Deliv Rev. 2012;64:194–205.

    Article  Google Scholar 

  32. Joshi A, Solanki S, Chaudhari R, Bahadur D, Aslam M, Srivastava R. Multifunctional alginate microspheres for biosensing, drug delivery and magnetic resonance imaging. Acta Biomater. 2011;7(11):3955–63.

    Article  Google Scholar 

  33. Soni ML, Kumar M, Namdeo K. Sodium alginate microspheres for extending drug release: formulation and in vitro evaluation. Int J Drug Deliv. 2011;2(1):64–68.

    Article  Google Scholar 

  34. Hegge AB, Andersen T, Melvik J, Kristensen S, Tønnesen H. Evaluation of novel alginate foams as drug delivery systems in antimicrobial photodynamic therapy (aPDT) of infected wounds—an in vitro study: studies on curcumin and curcuminoides XL. J Pharm Sci. 2010;99(8):3499–513.

    Article  Google Scholar 

  35. Yang J, Chen J, Pan D, Wan Y, Wang Z. pH-sensitive interpenetrating network hydrogels based on chitosan derivatives and alginate for oral drug delivery. Carbohydr Polym. 2013;92(1):719–25.

    Article  Google Scholar 

  36. Ghahramanpoor MK, Najafabadi SAH, Abdouss M, Bagheri F, Eslaminejad MB. A hydrophobically-modified alginate gel system: utility in the repair of articular cartilage defects. J Mater Sci—Mater Med. 2011;22(10):2365–75.

    Article  Google Scholar 

  37. Chavanpatil MD, Khdair A, Panyam J. Surfactant-polymer nanoparticles: a novel platform for sustained and enhanced cellular delivery of water-soluble molecules. Pharm Res. 2007;24(4):803–10.

    Article  Google Scholar 

  38. Lo C-L, Huang C-K, Lin K-M, Hsiue G-H. Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery. Biomaterials. 2007;28(6):1225–35.

    Article  Google Scholar 

  39. Gao Y, Li LB, Zhai G. Preparation and characterization of Pluronic/TPGS mixed micelles for solubilization of camptothecin. Colloids Surf, B. 2008;64(2):194–9.

    Article  Google Scholar 

  40. Kanti P, Srigowri K, Madhuri J, Smitha B, Sridhar S. Dehydration of ethanol through blend membranes of chitosan and sodium alginate by pervaporation. Sep Purif Technol. 2004;40(3):259–66.

    Article  Google Scholar 

  41. Smitha B, Sridhar S, Khan A. Chitosan–sodium alginate polyion complexes as fuel cell membranes. Eur Polym J. 2005;41(8):1859–66.

    Article  Google Scholar 

  42. Zohuriaan M, Shokrolahi F. Thermal studies on natural and modified gums. Polym Test. 2004;23(5):575–9.

    Article  Google Scholar 

  43. Shimizu T, Takada A. Preparation of Bi-based superconducting fiber by metal biosorption of Na-alginate. Polym Gels Netw. 1997;5(3):267–83.

    Article  Google Scholar 

  44. Desai MP, Labhasetwar V, Walter E, Levy RJ, Amidon GL. The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm Res. 1997;14(11):1568–73.

    Article  Google Scholar 

  45. Hillyer JF, Albrecht RM. Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci. 2001;90(12):1927–36.

    Article  Google Scholar 

  46. Brooking J, Davis S, Illum L. Transport of nanoparticles across the rat nasal mucosa. J Drug Target. 2001;9(4):267–79.

    Article  Google Scholar 

  47. Florence A, Hillery A, Hussain N, Jani P. Factors affecting the oral uptake and translocation of polystyrene nanoparticles: histological and analytical evidence. J Drug Target. 1995;3(1):65–70.

    Article  Google Scholar 

  48. Han J, Davis SS, Washington C. Physical properties and stability of two emulsion formulations of propofol. Int J Pharm. 2001;215(1):207–20.

    Article  Google Scholar 

  49. Baker MT, Naguib M. Propofol: the challenges of formulation. Anesthesiology. 2005;103(4):860–76.

    Article  Google Scholar 

  50. Finkelstein A, Lokhandwala BS, Pandey NS. Particulate contamination of an intact glass ampule. Anesthesiology. 1990;73(2):362–3.

    Article  Google Scholar 

  51. Chung H, Kim TW, Kwon M, Kwon IC, Jeong SY. Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system. J Control Release. 2001;71(3):339–50.

    Article  Google Scholar 

  52. Hung C-F, Fang C-L, Liao M-H, Fang J-Y. The effect of oil components on the physicochemical properties and drug delivery of emulsions: tocol emulsion versus lipid emulsion. Int J Pharm. 2007;335(1):193–202.

    Article  Google Scholar 

  53. Kandadi P, Syed MA, Goparaboina S, Veerabrahma K. Brain specific delivery of pegylated indinavir submicron lipid emulsions. Eur J Pharm Sci. 2011;42(4):423–32.

    Article  Google Scholar 

  54. Li X, Zhang Y, Fan Y, Zhou Y, Wang X, Fan C, et al. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol. Nanoscale Res Lett. 2011;6(1):1–9.

    Google Scholar 

  55. Arndt J, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. The J Physiol. 1991;440(1):467–78.

    Article  Google Scholar 

  56. Floyd AG. Top ten considerations in the development of parenteral emulsions. Pharm Sci Technol Today. 1999;2(4):134–43.

    Article  Google Scholar 

  57. Ilium L, Davis S, Wilson C, Thomas N, Frier M, Hardy J. Blood clearance and organ deposition of intravenously administered colloidal particles. The effects of particle size, nature and shape. Int J Pharm. 1982;12(2):135–46.

    Article  Google Scholar 

  58. Driscoll DF. Lipid injectable emulsions: pharmacopeial and safety issues. Pharm Res. 2006;23(9):1959–69.

    Article  Google Scholar 

  59. Geyer RP. Parenteral nutrition. Physiol Rev. 1960;40(1):150–86.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Young Researchers and Elite Club, South Tehran Branch, Islamic Azad University, Tehran, Iran

    Alireza Hassani Najafabadi, Saman Azodi-Deilami & Sina Farzaneh

  2. Department of Chemistry, Amirkabir University of Technology, P.O. Box 1587-4413, Tehran, Iran

    Majid Abdouss & Hamid Payravand

Authors
  1. Alireza Hassani Najafabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saman Azodi-Deilami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Majid Abdouss
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamid Payravand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sina Farzaneh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Alireza Hassani Najafabadi or Majid Abdouss.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hassani Najafabadi, A., Azodi-Deilami, S., Abdouss, M. et al. Synthesis and evaluation of hydroponically alginate nanoparticles as novel carrier for intravenous delivery of propofol. J Mater Sci: Mater Med 26, 145 (2015). https://doi.org/10.1007/s10856-015-5452-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-015-5452-0

Keywords

Search

Navigation