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Application of EPR-spin Probes to Evaluate Penetration Efficiency, Storage Capacity of Nanotransporters, and Drug Release

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Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin

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Abstract

Intensive research is required for the development of carrier systems that promote skin penetration of active compounds. These drugs have to be delivered selectively and in sufficient amounts to the site of interest. Therefore, the physicochemical properties of the drug-loaded carrier systems must be fully understood. Electron paramagnetic resonance (EPR) spectroscopy is a powerful tool to investigate the distribution of labeled drugs or drug analogs within a carrier to follow the penetration process and to determine the penetration efficiency. In this chapter we outline the fundamentals of EPR spectroscopy with particular focus on its applications in dermatopharmacology. We describe investigations with invasomes (ultraflexible liposomes), polymeric-based core-multishell nanotransporters, and nanostructured lipid carriers. These delivery systems were prepared or loaded with EPR-spin probes, and spin probe location within or on the carrier was investigated as well as their penetration properties.

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References

  • Alecci M, Ferrari M, Quaresima V, Sotgiu A, Ursini CL (1994) Simultaneous 280 MHz EPR imaging of rat organs during nitroxide free radical clearance. Biophys J 67(3):1274–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bobko AA, Kirilyuk IA, Gritsan NP, Polovyanenko DN, Grigor’ev IA, Khramtsov VV et al (2010) EPR and quantum chemical studies of the pH-sensitive imidazoline and imidazolidine nitroxides with bulky substituents. Appl Magn Reson 39(4):437–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braem C, Blaschke T, Panek-Minkin G, Herrmann W, Schlupp P, Paepenmuller T et al (2007) Interaction of drug molecules with carrier systems as studied by parelectric spectroscopy and electron spin resonance. J Control Release 119(1):128–135

    Article  CAS  PubMed  Google Scholar 

  • Burks SR, Legenzov EA, Rosen GM, Kao JP (2011) Clearance and biodistribution of liposomally encapsulated nitroxides: a model for targeted delivery of electron paramagnetic resonance imaging probes to tumors. Drug Metab Dispos Biol Fate Chem 39(10):1961–1966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cevc G, Schätzlein A, Richardsen H (2002) Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements. Biochim Biophys Acta 1564(1):21–30

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Liu X, Fahr A (2011) Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: in vitro study with finite and infinite dosage application. Int J Pharm 408(1–2):223–234

    Article  CAS  PubMed  Google Scholar 

  • Dragicevic-Curic N, Scheglmann D, Albrecht V, Fahr A (2008) Temoporfin-loaded invasomes: development, characterization and in vitro skin penetration studies. J Control Release 127(1):59–69

    Article  CAS  PubMed  Google Scholar 

  • Dragicevic-Curic N, Scheglmann D, Albrecht V, Fahr A (2009) Development of different temoporfin-loaded invasomes-novel nanocarriers of temoporfin: characterization, stability and in vitro skin penetration studies. Colloids Surf B Biointerfaces 70(2):198–206

    Article  CAS  PubMed  Google Scholar 

  • El Maghraby GM, Williams AC, Barry BW (2001) Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro. J Pharm Pharmacol 53(8):1069–1077

    Article  PubMed  Google Scholar 

  • Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM (2007) Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm 332(1–2):1–16

    Article  CAS  PubMed  Google Scholar 

  • Fuchs J, Freisleben HJ, Podda M, Zimmer G, Milbradt R, Packer L (1993) Nitroxide radical biostability in skin. Free Radic Biol Med 15(4):415–423

    Article  CAS  PubMed  Google Scholar 

  • Fuchs J, Groth N, Herrling T, Zimmer G (1997) Electron paramagnetic resonance studies on nitroxide radical 2,2,5,5-tetramethyl-4-piperidin-1-oxyl (TEMPO) redox reactions in human skin. Free Radic Biol Med 22(6):967–976

    Article  CAS  PubMed  Google Scholar 

  • Fuchs J, Herrling T, Groth N (2001) Detection of free radicals in skin: a review of the literature and new developments. Curr Probl Dermatol 29:1–17

    Article  CAS  PubMed  Google Scholar 

  • Fuchs MR, Schleicher E, Schnegg A, Kay CWM, Törring JT, Bittl R et al (2002) g-tensor of the neutral flavin radical cofactor of DNA photolyase revealed by 360-GHz electron paramagnetic resonance spectroscopy. J Phys Chem B 106(34):8885–8890

    Article  CAS  Google Scholar 

  • Gagua AV, Malenkov GG, Timofeev VP (1978) Hydrogen-bond contribution to isotropic hyperfine splitting constant of a nitroxide free radical. Chem Phys Lett 56(3):470–473

    Article  CAS  Google Scholar 

  • Haag SF, Chen M, Peters D, Keck CM, Taskoparan B, Fahr A et al (2011a) Nanostructured lipid carriers as nitroxide depot system measured by electron paramagnetic resonance spectroscopy. Int J Pharm 421:364–369

    Article  CAS  PubMed  Google Scholar 

  • Haag SF, Fleige E, Chen M, Fahr A, Teutloff C, Bittl R et al (2011b) Skin penetration enhancement of core-multishell nanotransporters and invasomes measured by electron paramagnetic resonance spectroscopy. Int J Pharm 416(1):223–228

    CAS  PubMed  Google Scholar 

  • Haag SF, Taskoparan B, Bittl R, Teutloff C, Wenzel R, Fahr A et al (2011c) Stabilization of reactive nitroxides using invasomes to allow prolonged electron paramagnetic resonance measurements. Skin Pharmacol Physiol 24(6):312–321

    Article  CAS  PubMed  Google Scholar 

  • Honeywell-Nguyen PL, de Graaff AM, Groenink HW, Bouwstra JA (2002) The in vivo and in vitro interactions of elastic and rigid vesicles with human skin. Biochim Biophys Acta 1573(2):130–140

    Article  CAS  PubMed  Google Scholar 

  • Jores K, Mehnert W, Drechsler M, Bunjes H, Johann C, Mäder K (2004) Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. J Control Release 95(2):217–227

    Article  CAS  PubMed  Google Scholar 

  • Keilitz J, Schwarze M, Nowag S, Schomäcker R, Haag R (2010) Homogeneous stabilization of Pt nanoparticles in dendritic core-multishell architectures: application in catalytic hydrogenation reactions and recycling. ChemCatChem 2(7):863–870

    Article  CAS  Google Scholar 

  • Kempe S, Metz H, Mader K (2010) Application of electron paramagnetic resonance (EPR) spectroscopy and imaging in drug delivery research – chances and challenges. Eur J Pharm Biopharm 74(1):55–66

    Article  CAS  PubMed  Google Scholar 

  • Khan N, Blinco JP, Bottle SE, Hosokawa K, Swartz HM, Micallef AS (2011) The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry. J Magn Reson 211(2):170–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirjavainen M, Urtti A, Jääskeläinen I, Suhonen TM, Paronen P, Valjakka-Koskela R et al (1996) Interaction of liposomes with human skin in vitro – the influence of lipid composition and structure. Biochim Biophys Acta 1304(3):179–189

    Article  CAS  PubMed  Google Scholar 

  • Küchler S, Abdel-Mottaleb M, Lamprecht A, Radowski MR, Haag R, Schäfer-Korting M (2009a) Influence of nanocarrier type and size on skin delivery of hydrophilic agents. Int J Pharm 377(1–2):169–172

    Article  PubMed  Google Scholar 

  • Küchler S, Radowski MR, Blaschke T, Dathe M, Plendl J, Haag R et al (2009b) Nanoparticles for skin penetration enhancement – a comparison of a dendritic core-multishell-nanotransporter and solid lipid nanoparticles. Eur J Pharm Biopharm 71(2):243–250

    Article  PubMed  Google Scholar 

  • Lombardi Borgia S, Regehly M, Sivaramakrishnan R, Mehnert W, Korting HC, Danker K et al (2005) Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy. J Control Release 110(1):151–163

    Article  CAS  PubMed  Google Scholar 

  • Martini G, Ciani L (2009) Electron spin resonance spectroscopy in drug delivery. Phys Chem Chem Phys 11(2):211–254

    Article  CAS  PubMed  Google Scholar 

  • Martini G, Bindi M, Ottaviani MF, Romanelli M (1985) Dipolar and spin exchange effects in the electron-spin-resonance spectra of nitroxide radicals in solution.2. Water solutions adsorbed on porous silica-gels. J Colloid Interface Sci 108(1):140–148

    Article  CAS  Google Scholar 

  • Mezei M, Gulasekharam V (1980) Liposomes – a selective drug delivery system for the topical route of administration. Lotion dosage form. Life Sci 26(18):1473–1477

    Article  CAS  PubMed  Google Scholar 

  • Müller RH, Jenning V, Mäder K, Lippacher A, Inventors (2000) Lipid particles on the basis of mixtures of liquid and solid lipids and methods for producing same. Germany

    Google Scholar 

  • Müller RH, Radtke M, Wissing SA (2002) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54(Suppl 1):S131–S155

    Article  PubMed  Google Scholar 

  • Obata Y, Takayama K, Okabe H, Nagai T (1990) Effect of cyclic monoterpenes on percutaneous absorption in the case of a water-soluble drug (diclofenac sodium). Drug Des Deliv 6(4):319–328

    CAS  PubMed  Google Scholar 

  • Obata Y, Takayama K, Machida Y, Nagai T (1991) Combined effect of cyclic monoterpenes and ethanol on percutaneous absorption of diclofenac sodium. Drug Des Discov 8(2):137–144

    CAS  PubMed  Google Scholar 

  • Ota Y, Hamada A, Nakano M, Saito H (2003) Evaluation of percutaneous absorption of midazolam by terpenes. Drug Metab Pharmacokinet 18(4):261–266

    Article  CAS  PubMed  Google Scholar 

  • Quadir MA, Radowski MR, Kratz F, Licha K, Hauff P, Haag R (2008) Dendritic multishell architectures for drug and dye transport. J Control Release 132(3):289–294

    Article  CAS  PubMed  Google Scholar 

  • Radowski MR, Shukla A, von Berlepsch H, Böttcher C, Pickaert G, Rehage H et al (2007) Supramolecular aggregates of dendritic multishell architectures as universal nanocarriers. Angew Chem Int Ed Engl 46(8):1265–1269

    Article  CAS  PubMed  Google Scholar 

  • Schäfer-Korting M, Mehnert W, Korting HC (2007) Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev 59(6):427–443

    Article  PubMed  Google Scholar 

  • Schätzlein A, Cevc G (1998) Non-uniform cellular packing of the stratum corneum and permeability barrier function of intact skin: a high-resolution confocal laser scanning microscopy study using highly deformable vesicles (Transfersomes). Br J Dermatol 138(4):583–592

    Article  PubMed  Google Scholar 

  • Smirnov AI, Smirnova TI, Morse PD 2nd (1995) Very high frequency electron paramagnetic resonance of 2,2,6,6-tetramethyl-1-piperidinyloxy in 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine liposomes: partitioning and molecular dynamics. Biophys J 68(6):2350–2360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Souto EB, Wissing SA, Barbosa CM, Müller RH (2004) Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery. Int J Pharm 278(1):71–77

    Article  CAS  PubMed  Google Scholar 

  • Stecova J, Mehnert W, Blaschke T, Kleuser B, Sivaramakrishnan R, Zouboulis CC et al (2007) Cyproterone acetate loading to lipid nanoparticles for topical acne treatment: particle characterisation and skin uptake. Pharm Res 24(5):991–1000

    Article  CAS  PubMed  Google Scholar 

  • Stoll S, Schweiger A (2006) EasySpin, a comprehensive software package for spectral simulation and analysis in EPR. J Magn Reson 178(1):42–55

    Article  CAS  PubMed  Google Scholar 

  • Treiber C, Quadir MA, Voigt P, Radowski M, Xu S, Munter LM et al (2009) Cellular copper import by nanocarrier systems, intracellular availability, and effects on amyloid beta peptide secretion. Biochemistry (Mosc) 48(20):4273–4284

    Article  CAS  Google Scholar 

  • van den Bergh BA, Bouwstra JA, Junginger HE, Wertz PW (1999) Elasticity of vesicles affects hairless mouse skin structure and permeability. J Control Release 62(3):367–379

    Article  PubMed  Google Scholar 

  • Velan SS, Spencer RG, Zweier JL, Kuppusamy P (2000) Electron paramagnetic resonance oxygen mapping (EPROM): direct visualization of oxygen concentration in tissue. Magn Reson Med 43(6):804–809

    Article  CAS  PubMed  Google Scholar 

  • Yucel U, Elias RJ, Coupland JN (2012) Solute distribution and stability in emulsion-based delivery systems: an EPR study. J Colloid Interface Sci 377(1):105–113

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work was funded by the Freie Universität (FU) Berlin, Focus Area Functional Nanoscale Materials. Furthermore, we thank Ming Chen and Alfred Fahr (Department of Pharmacy, Friedrich-Schiller-Universität Jena) for providing the invasomes, Emanuel Fleige and Rainer Haag (Department of Chemistry, FU-Berlin) for providing the CMS-nanotransporters, and Daniel Peters and Cornelia Keck (Department of Pharmacy, FU-Berlin) for providing the nanostructured lipid carriers. We also thank Robert Bittl and Christian Teutloff (Department of Physics, FU-Berlin) for Q- and W-band measurements as well as their valuable support regarding spectra analysis, and Monika Schäfer-Korting (Department of Pharmacy, FU-Berlin) for fruitful discussions.

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Authors and Affiliations

  1. Department of Dermatology, Venereology and Allergy, Charité – Universitätsmedizin Berlin, Center of Experimental and Applied Cutaneous Physiology, 10117, Berlin, Germany

    Stefan F. Haag, Jürgen Lademann & Martina C. Meinke

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  1. Stefan F. Haag
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  2. Jürgen Lademann
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  3. Martina C. Meinke
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Correspondence to Martina C. Meinke .

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  1. Apoteka “Beograd”, Belgrade, Serbia

    Nina Dragicevic

  2. San Francisco, California, USA

    Howard I. Maibach

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Haag, S.F., Lademann, J., Meinke, M.C. (2017). Application of EPR-spin Probes to Evaluate Penetration Efficiency, Storage Capacity of Nanotransporters, and Drug Release. In: Dragicevic, N., I. Maibach, H. (eds) Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53270-6_12

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  • DOI: https://doi.org/10.1007/978-3-662-53270-6_12

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