Advertisement

AAPS PharmSciTech

, 20:15 | Cite as

Active Targeting of Drugs and Bioactive Molecules via Oral Administration by Ligand-Conjugated Lipidic Nanocarriers: Recent Advances

  • A. B. Shreya
  • Sushil Yadaorao Raut
  • Renuka Suresh Managuli
  • Nayanabhirama Udupa
  • Srinivas MutalikEmail author
Review Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
  • 110 Downloads
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery

Abstract

The oral route is the most widely accepted and commonly used route for administration. However, this route may not be suitable for certain drug candidates which suffer from the problem of low aqueous solubility and gastrointestinal absorption and extensive first-pass effect. Nanotechnology-based approaches can be taken up as remedies to overcome the disadvantages associated with the oral route. Among the various nanocarriers, lipidic nanocarriers are widely used for oral delivery of bioactive molecules owing to their several advantages. Active targeting of bioactive molecules via lipidic nanocarriers has also been widely attempted to improve oral bioavailability and to avoid first-pass effect. This active targeting approach involves the use of ligands grafted or conjugated onto a nanocarrier that is specific to the receptors. Active targeting increases the therapeutic efficacy as well as reduces the toxic side effects of the drug or bioactive molecules. This review mainly focuses on the challenges involved in the oral delivery of drugs and its approaches to overcome the challenges using nanotechnology, specifically focusing on lipidic nanocarriers like liposomes, solid lipid nanoparticles, and nanostructured lipid carriers and active targeting of drug molecules by making use of ligand-conjugated lipidic nanocarriers.

KEY WORDS

lipidic nanocarriers liposomes nanostructured lipid carriers oral route active targeting 

Notes

References

  1. 1.
    Moss DM, Curley P, Kinvig H, Hoskins C, Owen A. The biological challenges and pharmacological opportunities of orally administered nanomedicine delivery. Expert Rev Gastroenterol Hepatol. 2018;12(3):223–36.PubMedGoogle Scholar
  2. 2.
    Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv Drug Deliv Rev. 2012;64(6):557–70.PubMedGoogle Scholar
  3. 3.
    Ghosh S, Roy T. Nanoparticulate drug-delivery systems: lymphatic uptake and its gastrointestinal applications. J Appl Pharm Sci. 2014;4(6):123–30.Google Scholar
  4. 4.
    Plapied L, Duhem N, des Rieux A, Préat V. Fate of polymeric nanocarriers for oral drug delivery. Curr Opin Colloid Interface Sci. 2011;16(3):228–37.Google Scholar
  5. 5.
    Bernkop-Schnürch A. Reprint of: Nanocarrier systems for oral drug delivery: do we really need them? Eur J Pharm Sci. 2013;50(1):2–7.PubMedGoogle Scholar
  6. 6.
    Agrawal AK, Harde H, Thanki K, Jain S. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration. Biomacromolecules. 2013;15(1):350–60.PubMedGoogle Scholar
  7. 7.
    Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev. 2009;61(2):158–71.PubMedGoogle Scholar
  8. 8.
    Sandzen B, Blom H, Dahlgren S. Gastric mucus gel layer thickness mearured by direct light microscopy. An experimental study in the rat. Scand J Gastroenterol. 1988;23(10):1160–4.PubMedGoogle Scholar
  9. 9.
    Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4(1):45–60.PubMedGoogle Scholar
  10. 10.
    Shahbazi M-A, Santos A, Improving Oral H. Absorption via drug-loaded nanocarriers: absorption mechanisms, intestinal models and rational fabrication. Curr Drug Metab. 2013;14(1):28–56.PubMedGoogle Scholar
  11. 11.
    Vllasaliu D, Fowler R, Garnett M, Eaton M, Stolnik S. Barrier characteristics of epithelial cultures modelling the airway and intestinal mucosa: a comparison. Biochem Biophys Res Commun. 2011;415(4):579–85.PubMedGoogle Scholar
  12. 12.
    Sonaje K, Chuang EY, Lin KJ, Yen TC, Su FY, Tseng MT, et al. Opening of epithelial tight junctions and enhancement of paracellular permeation by chitosan: microscopic, ultrastructural, and computed-tomographic observations. Mol Pharm. 2012;9(5):1271–9.PubMedGoogle Scholar
  13. 13.
    Tyagi P, Subramony JA. Nanotherapeutics in oral and parenteral drug delivery: key learnings and future outlooks as we think small. J Control Release. 2018;272(January):159–68.PubMedGoogle Scholar
  14. 14.
    Öztürk-Atar K, Eroğlu H, Çalış S. Novel advances in targeted drug delivery. J Drug Target. 2018;26(8):633–42.PubMedGoogle Scholar
  15. 15.
    Elbayoumi TA, Torchilin VP. Tumor-specific antibody-mediated targeted delivery of Doxil reduces the manifestation of auricular erythema side effect in mice. Int J Pharm. 2008;357(1–2):272–9.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Sala M, Diab R, Elaissari A, Fessi H. Lipid nanocarriers as skin drug delivery systems: properties, mechanisms of skin interactions and medical applications. Int J Pharm. 2018;535(1–2):1–17.PubMedGoogle Scholar
  17. 17.
    Haghiralsadat F, Amoabediny G, Naderinezhad S. Overview of preparation methods of polymeric and lipid-based (noisome, solid lipid, liposome) nanoparticles: a comprehensive review. 2018;6(4):383–400.Google Scholar
  18. 18.
    Attama AA, Momoh MA, Builders PF. Lipid nanoparticulate drug delivery systems : a revolution in dosage form design and development. 2012;Google Scholar
  19. 19.
    Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2–25.PubMedGoogle Scholar
  20. 20.
    Schwarz C, Mehnert W, Lucks JS, Miiller RH. Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J Control Release. 1994;30(93):83–96.Google Scholar
  21. 21.
    Buse J. Properties, engineering and applications of lipid-based nanoparticle drug-delivery systems: current research and advances. Nanomedicine. 2010;5:1237–60.PubMedGoogle Scholar
  22. 22.
    Mäder K, Mehnert W. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2–3):165–96.PubMedGoogle Scholar
  23. 23.
    Domingo C, Saurina J. An overview of the analytical characterization of nanostructured drug delivery systems: towards green and sustainable pharmaceuticals: a review. Anal Chim Acta. 2012;744:8–22.PubMedGoogle Scholar
  24. 24.
    Gaba B, Fazil M, Ali A, Baboota S, Sahni JK, Ali J. Nanostructured lipid (NLCs) carriers as a bioavailability enhancement tool for oral administration. Drug Deliv. 2015;22(6):691–700.PubMedGoogle Scholar
  25. 25.
    Jaiswal P, Gidwani B, Vyas A. Nanostructured lipid carriers and their current application in targeted drug delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):27–40.PubMedGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    He H, Lu Y, Qi J, Zhu Q, Chen Z, Wu W. Adapting liposomes for oral drug delivery. Acta Pharm Sin B. 2018;20.Google Scholar
  28. 28.
    Filatova LY, Klyachko NL, Kudryashova EV. Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors. Russ Chem Rev. 2018;87(4):374–91.Google Scholar
  29. 29.
    Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):102.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Chono S, Kaneko K, Yamamoto E, Togami K, Morimoto K. Effect of surface-mannose modification on aerosolized liposomal delivery to alveolar macrophages. Drug Dev Ind Pharm. 2010;36(1):102–7.PubMedGoogle Scholar
  31. 31.
    Martins S, Sarmento B, Ferreira DC, Souto EB. Lipid-based colloidal carriers for peptide and protein delivery–liposomes versus lipid nanoparticles. Int J Nanomedicine. 2007;2(4):595–607.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145–60.PubMedGoogle Scholar
  33. 33.
    Wu W, Lu Y, Qi J. Oral delivery of liposomes. Ther Deliv. 2015;6(11):1239–41.PubMedGoogle Scholar
  34. 34.
    des Rieux A, Pourcelle V, Cani PD, Marchand-Brynaert J, Préat V. Targeted nanoparticles with novel non-peptidic ligands for oral delivery. Adv Drug Deliv Rev. 2013;65(6):833–44.PubMedGoogle Scholar
  35. 35.
    Hamman JH, Demana PH, Olivier EI. Targeting receptors, transporters and site of absorption to improve oral drug delivery. Drug Target Insights. 2007;2:71–81.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Roger E, Lagarce F, Garcion E, Benoit JP. Biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery. Nanomedicine. 2010;5(2):287–306.PubMedGoogle Scholar
  37. 37.
    Khan AA, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations. Int J Nanomedicine. 2013;8:2733–44.PubMedCentralGoogle Scholar
  38. 38.
    Harde H, Das M, Jain S. Solid lipid nanoparticles: an oral bioavailability enhancer vehicle. Expert Opin Drug Deliv. 2011;8(11):1407–24.PubMedGoogle Scholar
  39. 39.
    Managuli RS, Raut SY, Reddy MS, Mutalik S. Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs. Expert Opin Drug Deliv. 2018;15(8):787–804.PubMedGoogle Scholar
  40. 40.
    Tsuji A, Tamai I. Carrier-mediated intestinal transport of drugs. Pharm Res. 1996;13(7):963–77.PubMedGoogle Scholar
  41. 41.
    Li X, Yu M, Fan W, Gan Y, Hovgaard L, Yang M. Orally active-targeted drug delivery systems for proteins and peptides. Expert Opin Drug Deliv. 2014;11(9):1435–47.PubMedGoogle Scholar
  42. 42.
    Zhang N, Ping QN, Huang GH, Han X, Cheng Y, Xu W. Transport characteristics of wheat germ agglutinin-modified insulin-liposomes and solid lipid nanoparticles in a perfused rat intestinal model. J Nanosci Nanotechnol. 2006;6(9–10):2959–66.PubMedGoogle Scholar
  43. 43.
    Zhang ZH, Zhang YL, Zhou JP, Lv HX. Solid lipid nanoparticles modified with stearic acid–octaarginine for oral administration of insulin. Int J Nanomedicine. 2012;7:3333.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Fan T, Chen C, Guo H, Xu J, Zhang J, Zhu X, et al. Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs. Eur J Pharm Biopharm. 2014;88(2):518–28.PubMedGoogle Scholar
  45. 45.
    Pooja D, Kulhari H, Kuncha M, Rachamalla SS, Adams DJ, Bansal V, et al. Improving efficacy, oral bioavailability, and delivery of paclitaxel using protein-grafted solid lipid nanoparticles. Mol Pharm. 2016;13(11):3903–12.PubMedGoogle Scholar
  46. 46.
    Xu Y, Zheng Y, Wu L, Zhu X, Zhang Z, Huang Y. Novel solid lipid nanoparticle with endosomal escape function for oral delivery of insulin. ACS Appl Mater Interfaces. 2018;10(11):9315–24.PubMedGoogle Scholar
  47. 47.
    Chen Y, Yuan L, Zhou L, Zhang ZH, Cao W, Wu Q. Effect of cell-penetrating peptide-coated nanostructured lipid carriers on the oral absorption of tripterine. Int J Nanomedicine. 2012;7:4581.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Zhao C, Fan T, Yang Y, Wu M, Li L, Zhou Z, et al. Preparation, macrophages targeting delivery and anti-inflammatory study of pentapeptide grafted nanostructured lipid carriers. Int J Pharm. 2013;450(1–2):11–20.PubMedGoogle Scholar
  49. 49.
    Zhou X, Zhang X, Ye Y, Zhang T, Wang H, Ma Z, et al. Nanostructured lipid carriers used for oral delivery of oridonin: an effect of ligand modification on absorption. Int J Pharm. 2015;479(2):391–8.PubMedGoogle Scholar
  50. 50.
    Fang G, Tang B, Chao Y, Xu H, Gou J, Zhang Y, et al. Cysteine-functionalized nanostructured lipid carriers for oral delivery of docetaxel: a permeability and pharmacokinetic study. Mol Pharm. 2015;12(7):2384–95.PubMedGoogle Scholar
  51. 51.
    Tian C, Asghar S, Wu Y, Chen Z, Jin X, Yin L, et al. Improving intestinal absorption and oral bioavailability of curcumin via taurocholic acid-modified nanostructured lipid carriers. Int J Nanomedicine. 2017;12:7897–911.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Xia CQ, Wang J, Shen WC. Hypoglycemic effect of insulin-transferrin conjugate in streptozotocin induced diabetic rats. J Pharmacol Exp Ther. 2000;295:594–600.PubMedGoogle Scholar
  53. 53.
    Zhang N, Ping QN, Huang GH, Xu WF. Investigation of lectin-modified insulin liposomes as carriers for oral administration. Int J Pharm. 2005;294(1–2):247–59.PubMedGoogle Scholar
  54. 54.
    Ling SS, Yuen KH, Magosso E, Barker SA. Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats. J Pharm Pharmacol. 2009;61(4):445–9.PubMedGoogle Scholar
  55. 55.
    Pukanud P, Peungvicha P, Sarisuta N. Development of mannosylated liposomes for bioadhesive oral drug delivery via M cells of Peyer’s patches. Drug Deliv. 2009;16(5):289–94.PubMedGoogle Scholar
  56. 56.
    Li K, Zhao X, Xu S, Pang D, Yang C, Chen D. Application of Ulex europaeus agglutinin I-modified liposomes for oral vaccine: ex vivo bioadhesion and in vivo immunity. Chem Pharm Bull. 2011;59(5):618–23.PubMedGoogle Scholar
  57. 57.
    Gupta PN, Vyas SP. Investigation of lectinized liposomes as M-cell targeted carrier-adjuvant for mucosal immunization. Colloids Surf B: Biointerfaces. 2011;82(1):118–25.PubMedGoogle Scholar
  58. 58.
    Lo DD, Ling J, Eckelhoefer AH. M cell targeting by a Claudin 4 targeting peptide can enhance mucosal IgA responses. BMC Biotechnol. 2012;12(1):7.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Zhang X, Qi J, Lu Y, He W, Li X, Wu W. Biotinylated liposomes as potential carriers for the oral delivery of insulin. Nanomedicine. 2014;10(1):167–76.PubMedGoogle Scholar
  60. 60.
    Agrawal U, Sharma R, Gupta M, Vyas SP. Is nanotechnology a boon for oral drug delivery? Drug Discov Today. 2014;0(10):1530–46.Google Scholar
  61. 61.
    Yingsukwattana K, Puttipipatkhachorn S, Ruktanonchai U, Sarisuta N. Enhanced permeability across Caco-2 cell monolayers by specific mannosylating ligand of buserelin acetate proliposomes. J Liposome Res. 2016;26(1):69–79.PubMedGoogle Scholar
  62. 62.
    Zhang X, Qi J, Lu Y, He W, Li X, Wu W. Biotinylated liposomes as potential carriers for the oral delivery of insulin. Nanomedicine: nanotechnology, biology and medicine. 2014;10(1):167–76.Google Scholar
  63. 63.
    Fricker G, Kromp T, Wendel A, Blume A, Zirkel J, Rebmann H, et al. Phospholipids and lipid-based formulations in oral drug delivery. Pharm Res. 2010;27(8):1469–86.PubMedGoogle Scholar
  64. 64.
    Rogers JA, Anderson KE. The potential of liposomes in oral drug delivery. Crit Rev Ther Drug Carrier Syst. 1998;15(5):60.Google Scholar
  65. 65.
    Morishita M, Peppas NA. Is the oral route possible for peptide and protein drug delivery? Drug Discov Today. 2006;11(19–20):905–10.PubMedGoogle Scholar
  66. 66.
    Gabor F, Bogner E, Weissenboeck A, Wirth M. The lectin–cell interaction and its implications to intestinal lectin-mediated drug delivery. Adv Drug Deliv Rev. 2004;56(4):459–80.PubMedGoogle Scholar
  67. 67.
    Clark MA, Hirst BH, Jepson MA. Lectin-mediated mucosal delivery of drugs and microparticles. Adv Drug Deliv Rev. 2000;43(2–3):207–23.PubMedGoogle Scholar
  68. 68.
    Clark MA, Jepson MA, Simmons NL, Hirst BH. Differential surface characteristics of M cells from mouse intestinal Peyer’s and caecal patches. Histochem J. 1994;26:271–80.PubMedGoogle Scholar
  69. 69.
    Chen H, Torchilin V, Langer R. Lectin-bearing polymerized liposomes as potential oral vaccine carriers. Pharm Res. 1996;13(9):1378–83.PubMedGoogle Scholar
  70. 70.
    Wirth M, Kneuer C, Lehr CM, Gabor F. Lectin-mediated drug delivery: discrimination between cytoadhesion and cytoinvasion and evidence for lysosomal accumulation of wheat germ agglutinin in the Caco-2 model. J Drug Target. 2002;10(6):439–48.PubMedGoogle Scholar
  71. 71.
    Irache JM, Salman HH, Gamazo C, Espuelas S. Mannose-targeted systems for the delivery of therapeutics. Expert Opin Drug Deliv. 2008;5(6):703–24.PubMedGoogle Scholar
  72. 72.
    Takahashi K, Donovan MJ, Rogers RA, Ezekowitz RA. Distribution of murine mannose receptor expression from early embryogenesis through to adulthood. Cell Tissue Res. 1998;292(2):311–23.PubMedGoogle Scholar
  73. 73.
    Fievez V, Plapied L, des Rieux A, Pourcelle V, Freichels H, Wascotte V, et al. Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination. Eur J Pharm Biopharm. 2009;73(1):16–24.PubMedGoogle Scholar
  74. 74.
    Witoonsaridsilp W, Paeratakul O, Panyarachun B, Sarisuta N. Development of mannosylated liposomes using synthesized N-octadecyl-D-mannopyranosylamine to enhance gastrointestinal permeability for protein delivery. AAPS PharmSciTech. 2012;13(2):699–706.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Roger E, Kalscheuer S, Kirtane A, Guru BR, Grill AE, Whittum-Hudson J, et al. Folic acid functionalized nanoparticles for enhanced oral drug delivery. Mol Pharm. 2012;9(7):2103–10.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Chatterjee NS, Kumar CK, Ortiz A, Rubin SA, Said HM. Molecular mechanism of the intestinal biotin transport process. Am J Phys Cell Phys. 1999;277:C605–13.Google Scholar
  77. 77.
    Youn YS, Chae SY, Lee S, Kwon MJ, Shin HJ, Lee KC. Improved peroral delivery of glucagon-like peptide-1 by site-specific biotin modification: design, preparation, and biological evaluation. Eur J Pharm Biopharm. 2008;68(3):667–75.PubMedGoogle Scholar
  78. 78.
    Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM. Effect of folate over supplementation on folate uptake by human intestinal and renal epithelial cells. Am J Clin Nutr. 2007;86:159–66.PubMedGoogle Scholar
  79. 79.
    Anderson KE, Stevenson BR, Rogers JA. Folic acid–PEO-labeled liposomes to improve gastrointestinal absorption of encapsulated agents. J Control Release. 1999;60(2–3):189–98.PubMedGoogle Scholar
  80. 80.
    Banerjee D, Flanagan PR, Cluett J, Valberg LS. Transferrin receptors in the human gastrointestinal tract. Relationship to body iron stores. Gastroenterology. 1986;91:861–9.PubMedGoogle Scholar
  81. 81.
    Qing X, Yang X, Yang X, Qian Z, Kui W. Drug delivery via the transferrin receptor-mediated endocytosis pathway. J Chin Pharm Sci. 2009;18:7–13.Google Scholar
  82. 82.
    Zhang L, Shi Y, Song Y, Duan D, Zhang X, Sun K, et al. Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide. J Drug Target. 2018:1–0.Google Scholar
  83. 83.
    Shah D, Shen WC. Transcellular delivery of an insulin-transferrin conjugate in enterocyte-like Caco-2 cells. J Pharm Sci. 1996;85(12):1306–11.PubMedGoogle Scholar
  84. 84.
    Li H, Qian ZM. Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev. 2002;22:225–50.PubMedGoogle Scholar
  85. 85.
    Garinot M, Fiévez V, Pourcelle V, Stoffelbach F, des Rieux A, Plapied L, et al. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release. 2007;120(3):195–204.PubMedGoogle Scholar
  86. 86.
    KuoLee R, Chen W. M cell-targeted delivery of vaccines and therapeutics. Expert Opin Drug Deliv. 2008;5(6):693–702.PubMedGoogle Scholar
  87. 87.
    des Rieux A, Ragnarsson EG, Gullberg E, Préat V, Schneider YJ, Artursson P. Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. Eur J Pharm Sci. 2005;25(4–5):455–65.PubMedGoogle Scholar
  88. 88.
    Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev. 2013;65(6):822–32.PubMedGoogle Scholar
  89. 89.
    Gullberg E, Keita ÅV, Sa'ad YS, Andersson M, Caldwell KD, Söderholm JD, et al. Identification of cell adhesion molecules in the human follicle-associated epithelium that improve nanoparticle uptake into the Peyer’s patches. J Pharmacol Exp Ther. 2006;319(2):632–9.PubMedGoogle Scholar
  90. 90.
    Ding J, Feng M, Wang F, Wang H, Guan W. Targeting effect of PEGylated liposomes modified with the Arg-Gly-Asp sequence on gastric cancer. Oncol Rep. 2015;34(4):1825–34.PubMedGoogle Scholar
  91. 91.
    Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res. 2005;65(21):9603–6.PubMedGoogle Scholar
  92. 92.
    McClane BA, Chakrabarti G. New insights into the cytotoxic mechanisms of Clostridium perfringens enterotoxin. Anaerobe. 2004;10(2):107–14.PubMedGoogle Scholar
  93. 93.
    Ebihara C, Kondoh M, Hasuike N, Harada M, Mizuguchi H, Horiguchi Y, et al. Preparation of a claudin-targeting molecule using a C-terminal fragment of Clostridium perfringens enterotoxin. J Pharmacol Exp Ther. 2006 Jan 1;316(1):255–60.PubMedGoogle Scholar
  94. 94.
    Gao Z, McClane BA. Use of Clostridium perfringens enterotoxin and the enterotoxin receptor-binding domain (C-CPE) for cancer treatment: opportunities and challenges. J Toxicol. 2012;2012:1–9.Google Scholar
  95. 95.
    Yoshida M, Claypool SM, Wagner JS, Mizoguchi E, Mizoguchi A, Roopenian DC, et al. Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity. 2004;20:769–83.PubMedGoogle Scholar
  96. 96.
    Pridgen EM, Alexis F, Kuo TT, Levy-Nissenbaum E, Karnik R, Blumberg RS, et al. Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery. Sci Transl Med. 2013;5(213):213ra167.PubMedPubMedCentralGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • A. B. Shreya
    • 1
  • Sushil Yadaorao Raut
    • 1
  • Renuka Suresh Managuli
    • 1
  • Nayanabhirama Udupa
    • 2
  • Srinivas Mutalik
    • 1
    Email author
  1. 1.Department of Pharmaceutics, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia
  2. 2.Director - Research (Health Sciences), Manipal Academy of Higher EducationManipalIndia

Personalised recommendations