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Low Molecular Weight Micelles

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Fundamentals of Pharmaceutical Nanoscience

Abstract

Low molecular weight amphiphile micelles are formed from the self-assembly of comparatively hydrophilic amphiphiles (molecular weight >1,500 Da). These structures may be spherical or present as nanofibres in the case of peptide amphiphiles; the latter with one axis in the 5–20 nm size range. Micelles are formed from amphiphiles in aqueous media and micelle formation is driven by the need to reduce the energetically unfavourable interactions between the hydrophobic regions of the amphiphilic molecule and the bulk water molecules. Micelles are used for the delivery of hydrophobic drugs and are usually used in intravenous formulations. Hydrophobic drugs may be encapsulated within the hydrophobic micelle core, increasing the level of hydrophobic drug that may be incorporated within aqueous media by over 1,000-fold in some cases. The characterisation of micelles for pharmaceutical use involves a determination of: the critical micellar concentration (the concentration at which micellisation starts), the colloidal stability of the dispersion, micelle particle size, micelle morphology and the drug encapsulation or drug solubilisation capacity of the micellar dispersion. Micelles formed from low molecular weight amphiphiles are dynamic structures and there is continuous exchange of material between the micellar aggregate and the bulk medium; this dynamic exchange has a negative effect on the stability and biocompatibility of micellar formulations.

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References

  • Alvarez-Nunez FA, Yalkowsky SH (2000) Relationship between Polysorbate 80 solubilization descriptors and octanol-water partition coefficients of drugs. Int J Pharm 200:217–222

    Article  PubMed  CAS  Google Scholar 

  • Brajtburg J, Elberg S, Kobayashi GS, Bolard J (1994a) Amphotericin-b incorporated into egg lecithin bile-salt mixed micelles—molecular and cellular aspects relevant to therapeutic efficacy in experimental mycoses. Antimicrob Agent Chemother 38:300–306

    Article  CAS  Google Scholar 

  • Brajtburg J, Elberg S, Travis SJ, Kobayashi GS (1994b) Treatment of murine candidiasis and cryptococcosis with amphotericin-b incorporated into egg lecithin bile-salt mixed micelles. Antimicrob Agent Chemother 38:294–299

    Article  CAS  Google Scholar 

  • Buwalda RT, Engberts J (2001) Aggregation of dicationic surfactants with methyl orange in aqueous solution. Langmuir 17:1054–1059

    Article  CAS  Google Scholar 

  • Cheng LY, Hostetler KY, Gardner MF, Avila CP, Bergeron-Lynn G, Keefe KS, Wiley CA, Freeman WR (1999) Intravitreal toxicology in rabbits of two preparations of 1-O-octadecyl-sn-glycerol-3-phosphonoformate, a sustained-delivery anti-CMV drug. Investig Ophthalmol Vis Sci 40:1487–1495

    CAS  Google Scholar 

  • Chooi KW, Gray AI, Tetley L, Fan YL, Uchegbu IF (2010) The molecular shape of poly(propylenimine) dendrimers has a profound effect on their self assembly. Langmuir 26:2301–2316

    Article  PubMed  CAS  Google Scholar 

  • Cifuentes A, Bernal JL, DiezMasa JC (1997) Determination of critical micelle concentration values using capillary electrophoresis instrumentation. Anal Chem 69:4271–4274

    Article  CAS  Google Scholar 

  • Cui H, Webber MJ, Stupp SI (2010) Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials. Biopolymers 94:1–18

    Article  PubMed  CAS  Google Scholar 

  • Dailymed (2012) Fungizone—amphotericin B injection. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=426c9bf0-668e-46b2-ae2a-2def88a66269

  • Dal Bo AG, Soldi V, Giacomelli FC, Travelet C, Jean B, Pignot-Paintrand I, Borsali R, Fort S (2012) Self-assembly of amphiphilic glycoconjugates into lectin-adhesive nanoparticles. Langmuir 28:1418–1426

    Article  PubMed  CAS  Google Scholar 

  • Dimitrijevic D, Lamandin C, Uchegbu IF, Shaw AJ, Florence AT (1997) The effect of monomers and of micellar and vesicular forms of non-ionic surfactants (Solulan C24 and Solulan 16) on Caco-2 cell monolayers. J Pharm Pharmacol 49:611–616

    Article  PubMed  CAS  Google Scholar 

  • Echevarria I, Barturen C, Renedo MJ, Troconiz IF, Dios-Vieitez MC (2000) Comparative pharmacokinetics, tissue distributions, and effects on renal function of novel polymeric formulations of amphotericin B and amphotericin B-deoxycholate in rats. Antimicrob Agent Chemother 44:898–904

    Article  CAS  Google Scholar 

  • European Medicines Agency (2012) Reflection paper on the pharmaceutical development of intravenous medcinal products containing active substances solubilised in micellar systems. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/03/WC500124410.pdf

  • Florence AT, Attwood D (2006) Physicochemical principles of pharmacy. McMillan, London

    Google Scholar 

  • Gregoriadis G (2006) Liposome technology volumes I, II and III. CRC Press, Boca Raton

    Book  Google Scholar 

  • Hendradi E, Obata Y, Isowa K, Nagai T, Takayama K (2003) Effect of mixed micelle formulations including terpenes on the transdermal delivery of diclofenac. Biol Pharm Bull 26:1739–1743

    Article  PubMed  CAS  Google Scholar 

  • Hildebrand A, Garidel P, Neubert R, Blume B (2004) Thermodynamics of demicellisation of mixed micelles composed of sodium oleate and bile salts. Langmuir 20:320–328

    Article  PubMed  CAS  Google Scholar 

  • Israelachvili J (2011) Intermolecular & surface forces 3rd edition. Academic, Amsterdam

    Google Scholar 

  • Jain R, Nabar S, Dandekar P, Patravale V (2010) Micellar nanocarriers: potential nose-to-brain delivery of zolmitriptan as novel migraine therapy. Pharm Res 27:655–664

    Article  PubMed  CAS  Google Scholar 

  • Javali NM, Raj A, Saraf P, Li X, Jasti B (2012) Fatty acid-RGD peptide amphiphile micelles as potential paclitaxel delivery carriers to alpha(v)beta(3) integrin overexpressing tumors. Pharm Res 29:3347–3361

    Article  PubMed  CAS  Google Scholar 

  • Kalyanasundaram K, Thomas JK (1977) Environmental effects on vibrionic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems. J Am Chem Soc 99:2039–2044

    Article  CAS  Google Scholar 

  • Karukstis KK, Savin DA, Loftus CT, D’Angelo ND (1998) Spectroscopic studies of the interaction of methyl orange with cationic alkyltrimethylammonium bromide surfactants. J Colloid Interface Sci 203:157–163

    Article  CAS  Google Scholar 

  • Kirkpatrick P (2003) Pressures in the pipeline. Nat Rev Drug Discov 2:337

    Article  CAS  Google Scholar 

  • Laing ME, McBain JW (1920) The investigation of sodium oleate solutions in the three physical states of curd, gel, and sol. J Chem Soc 117:1506–1528

    Article  Google Scholar 

  • Lalatsa A, Schatzlein AG, Mazza M, Le TB, Uchegbu IF (2012) Amphiphilic poly(l-amino acids)—new materials for drug delivery. J Control Release 161:523–536

    Article  PubMed  CAS  Google Scholar 

  • Lasic DD (1992) Mixed micelles in drug delivery. Nature 355:279–280

    Article  PubMed  CAS  Google Scholar 

  • Li X, Zhang Y, Fan Y, Zhou Y, Wang X, Fan C, Liu Y, Zhang Q (2011) Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol. Nanoscale Res Lett 6:275

    Article  PubMed  Google Scholar 

  • Loguercio C, Festi D (2011) Silybin and the liver: from basic research to clinical practice. World J Gastroenterol 17:2288–2301

    Article  PubMed  CAS  Google Scholar 

  • Mandal AB, Nair BU, Ramaswamy D (1988) Determination of the critical micelle concentration of surfactants and the partition-coefficient of an electrochemical probe by using cyclic voltammetry. Langmuir 4:736–739

    Article  CAS  Google Scholar 

  • Matsuoka K, Moroi Y (2002) Micelle formation of sodium deoxycholate and sodium ursodeoxycholate (Part 1). Biochim Biophys Acta-Mol Cell Biol Lipids 1580:189–199

    Article  CAS  Google Scholar 

  • Mazza M, Notman R, Anwar J, Rodger A, Hicks M, Parkinson G, McCarthy D, Daviter T, Moger J, Garrett N, Mead T, Briggs M, Schatzlein AG, Uchegbu IF (2013) Nanofiber-based delivery of therapeutic peptides to the brain. ACS Nano 7:1016–1026

    Article  PubMed  CAS  Google Scholar 

  • Mclean LR, Krstenansky JL, Owen TJ, Eftink MR, Hagaman KA (1989) Effect of micelle diameter on tryptophan dynamics in an amphipathic helical peptide in phosphatidylcholine. Biochemistry 28:8403–8410

    Article  PubMed  CAS  Google Scholar 

  • Mehrotra KN, Jain M (1992) Conductivity, viscosity and ultrasonic studies of rubidium caprylate. Ind J Chem Sect A 31:452–456

    Google Scholar 

  • Nagadome S, Shibata O, Miyoshi H, Kagimoto H, Ikawa Y, Igimi H, Sugihara G (1992) Mixed systems of bile-salts—micellization and monolayer formation. ACS Symp Ser 501:301–315

    Article  CAS  Google Scholar 

  • Nema S, Washkuhn RJ, Brendel RJ (1997) Excipients and their use in injectable products. PDA J Pharm Sci Tech/PDA 51:166–171

    CAS  Google Scholar 

  • Okano LT, Quina FH, El Seoud OA (2000) Fluorescence and light-scattering studies of the aggregation of cationic surfactants in aqueous solution: effects of headgroup structure. Langmuir 16:3119–3123

    Article  CAS  Google Scholar 

  • Patist A, Bhagwat SS, Penfield KW, Aikens P, Shah DO (2000) On the measurement of critical micelle concentrations of pure and technical-grade nonionic surfactants. J Surfactants Deterg 3:53–58

    Article  CAS  Google Scholar 

  • Powell MF, Nguyen T, Baloian L (1998) Compendium of excipients for parenteral formulations. PDA J Pharm Sci Tech/PDA 52:238–311

    CAS  Google Scholar 

  • Ross BP, Braddy AC, McGeary RP, Blanchfield JT, Prokai L, Toth I (2004) Micellar aggregation and membrane partitioning of bile salts, fatty acids, sodium dodecyl sulfate, and sugar-conjugated fatty acids: correlation with hemolytic potency and implications for drug delivery. Mol Pharm 1:233–245

    Article  PubMed  CAS  Google Scholar 

  • Rowe RC, Sheskey PJ, Quinn ME (2009) Handbook of pharmaceutical excipients. Pharmaceutical Press, London

    Google Scholar 

  • Siew A, Le H, Thiovolet M, Gellert P, Schatzlein A, Uchegbu I (2012) Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles. Mol Pharm 9:14–28

    Article  PubMed  CAS  Google Scholar 

  • Soukasene S, Toft DJ, Moyer TJ, Lu HM, Lee HK, Standley SM, Cryns VL, Stupp SI (2011) Antitumor activity of peptide amphiphile nanofiber-encapsulated camptothecin. ACS Nano 5:9113–9121

    Article  PubMed  CAS  Google Scholar 

  • St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ (2001) Transport of bile acids in hepatic and non-hepatic tissues. J Exp Biol 204:1673–1686

    PubMed  CAS  Google Scholar 

  • Strickley RG (2004) Solubilizing excipients in oral and injectable formulations. Pharm Res 21:201–230

    Article  PubMed  CAS  Google Scholar 

  • Tanford C (1980) The hydrophobic effect: formation of micelles and biological membranes. Wiley, New York

    Google Scholar 

  • van Etten EWM, van Vianen W, Roovers P, Frederik P (2000) Mild heating of amphotericin B-desoxycholate: effects on ultrastructure, in vitro activity and toxicity, and therapeutic efficacy in severe candidiasis in leukopenic mice. Antimicrob Agent Chemother 44:1598–1603

    Article  Google Scholar 

  • Wang W, Qu XZ, Gray AI, Tetley L, Uchegbu IF (2004) Self-assembly of cetyl linear polyethylenimine to give micelles, vesicles, and dense nanoparticles. Macromolecules 37:9114–9122

    Article  CAS  Google Scholar 

  • Williams RJ, Phillips JN, Mysels KJ (1955) The critical micelle concentration of sodium lauryl sulphate at 25-degrees-C. Trans Faraday Soc 51:728–737

    Article  CAS  Google Scholar 

  • Yu JN, Zhu YA, Wang L, Peng M, Tong SS, Cao X, Qiu H, Xu XM (2010) Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol Sin 31:759–764

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Fung BM (1993) NMR-study of the transformation of sodium dodecyl-sulfate micelles. Langmuir 9:1228–1231

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK

    Ijeoma F. Uchegbu

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  1. Ijeoma F. Uchegbu
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Correspondence to Ijeoma F. Uchegbu .

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Editors and Affiliations

  1. UCL School of Pharmacy, University College London, London, United Kingdom

    Ijeoma F. Uchegbu

  2. UCL School of Pharmacy, University College London, London, United Kingdom

    Andreas G. Schätzlein

  3. Bexleyheath, United Kingdom

    Woei Ping Cheng

  4. School of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom

    Aikaterini Lalatsa

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Uchegbu, I.F. (2013). Low Molecular Weight Micelles. In: Uchegbu, I., Schätzlein, A., Cheng, W., Lalatsa, A. (eds) Fundamentals of Pharmaceutical Nanoscience. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9164-4_2

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