Skip to main content

Advertisement

Log in

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

  • Review Article
  • Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

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.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  3. Ghosh S, Roy T. Nanoparticulate drug-delivery systems: lymphatic uptake and its gastrointestinal applications. J Appl Pharm Sci. 2014;4(6):123–30.

    CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  9. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4(1):45–60.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  14. Öztürk-Atar K, Eroğlu H, Çalış S. Novel advances in targeted drug delivery. J Drug Target. 2018;26(8):633–42.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

  18. Attama AA, Momoh MA, Builders PF. Lipid nanoparticulate drug delivery systems : a revolution in dosage form design and development. 2012;

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  21. Buse J. Properties, engineering and applications of lipid-based nanoparticle drug-delivery systems: current research and advances. Nanomedicine. 2010;5:1237–60.

    CAS  PubMed  Google Scholar 

  22. Mäder K, Mehnert W. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2–3):165–96.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

  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.

    CAS  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145–60.

    CAS  PubMed  Google Scholar 

  33. Wu W, Lu Y, Qi J. Oral delivery of liposomes. Ther Deliv. 2015;6(11):1239–41.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  Google Scholar 

  38. Harde H, Das M, Jain S. Solid lipid nanoparticles: an oral bioavailability enhancer vehicle. Expert Opin Drug Deliv. 2011;8(11):1407–24.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  40. Tsuji A, Tamai I. Carrier-mediated intestinal transport of drugs. Pharm Res. 1996;13(7):963–77.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

  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.

    CAS  PubMed  Google Scholar 

  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. Morishita M, Peppas NA. Is the oral route possible for peptide and protein drug delivery? Drug Discov Today. 2006;11(19–20):905–10.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  69. Chen H, Torchilin V, Langer R. Lectin-bearing polymerized liposomes as potential oral vaccine carriers. Pharm Res. 1996;13(9):1378–83.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

  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.

    CAS  PubMed  Google Scholar 

  84. Li H, Qian ZM. Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev. 2002;22:225–50.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  86. KuoLee R, Chen W. M cell-targeted delivery of vaccines and therapeutics. Expert Opin Drug Deliv. 2008;5(6):693–702.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  91. Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res. 2005;65(21):9603–6.

    CAS  PubMed  Google Scholar 

  92. McClane BA, Chakrabarti G. New insights into the cytotoxic mechanisms of Clostridium perfringens enterotoxin. Anaerobe. 2004;10(2):107–14.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Srinivas Mutalik.

Additional information

Guest Editor: Sanyog Jain

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shreya, A.B., Raut, S.Y., Managuli, R.S. et al. Active Targeting of Drugs and Bioactive Molecules via Oral Administration by Ligand-Conjugated Lipidic Nanocarriers: Recent Advances. AAPS PharmSciTech 20, 15 (2019). https://doi.org/10.1208/s12249-018-1262-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-018-1262-2

KEY WORDS

Navigation