Skip to main content

Advertisement

Log in

Lipid-Based Nanocarriers for Lymphatic Transportation

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

Abstract

The effectiveness of any drug is dependent on to various factors like drug solubility, bioavailability, selection of appropriate delivery system, and proper route of administration. The oral route for the delivery of drugs is undoubtedly the most convenient, safest and has been widely used from past few decades for the effective delivery of drugs. However, despite of the numerous advantages that oral route offers, it often suffers certain limitations like low bioavailability due to poor water solubility as well as poor permeability of drugs, degradation of the drug in the physiological pH of the stomach, hepatic first-pass metabolism, etc. The researchers have been continuously working extensively to surmount and address appropriately the inherent drawbacks of the oral drug delivery. The constant and continuous efforts have led to the development of lipid-based nano drug delivery system to overcome the aforesaid associated challenges of the oral delivery through lymphatic transportation. The use of lymphatic route has demonstrated its critical and crucial role in overcoming the problem associated and related to low bioavailability of poorly water-soluble and poorly permeable drugs by bypassing intestinal absorption and possible first-pass metabolism. The current review summarizes the bonafide perks of using the lipid-based nanocarriers for the delivery of drugs using the lymphatic route. The lipid-based nanocarriers seem to be a promising delivery system which can be optimized and further explored as an alternative to the conventional dosage forms for the enhancement of oral bioavailability of drugs, with better patient compliance, minimum side effect, and improved the overall quality of life.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Sharma R, Agrawal U, Vyas SP. Polymeric nanocarriers for the oral delivery of bioactives. Curr Drug Deliv. 2014;9(1):21–34.

    CAS  Google Scholar 

  2. Stella VJ, Charman WN. Lymphatic transport of drugs. 1st ed. Florida: CRC Press; 1992.

    Google Scholar 

  3. Khan AA, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations. Int J Nanomedicine. 2013:2733–44.

  4. Cai S, Yang Q, Bagby TR, Forrest ML. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles. Adv Drug Deliv Rev. 2011;63(10–11):901–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Agrawal U, Sharma R, Mody N, Dubey S, Vyas SP. Improved oral bioavailability of bioactives through lipid-based nanoarchitectures. In: Grumezescu A, editor. Surface chemistry of nanobiomaterials: applications of nanobiomaterials. Volume 3. Cambridge: Willaim Andrew; 2016. p. 433–62.

    Google Scholar 

  6. Chaudhary S, Garg T, Murthy RSR, Rath G, Goyal AK. Recent approaches of lipid-based delivery system for lymphatic targeting via oral route. J Drug Target. 2014;2330:1–12.

    Google Scholar 

  7. Jain A, Gautam L, Vishwakarma N, Sharma R, Mody N, Dubey S, et al. Emergence of polymer-lipid hybrid systems in healthcare scenario. In: Multifunctional nanocarriers for contemporary healthcare applications. Hershey: IGI Global; 2018. p. 448–70.

    Google Scholar 

  8. Yáñez JA, Wang SWJ, Knemeyer IW, Wirth MA, Alton KB. Intestinal lymphatic transport for drug delivery. Adv Drug Deliv Rev. 2015;63(10–11):923–42.

    Google Scholar 

  9. Vyas SP, Jaitely V, Kanaujia P. Synthesis and characterisation of palymitoyl propanolol hydrochloride auto-lymphotrophs for oral administration. Int J Pharm. 1999;186:177–89.

    CAS  PubMed  Google Scholar 

  10. Bora CR, Prabhu RH, Patravale VB. Lymphatic delivery: concept, challenges and applications. Indian Drugs. 2017;8:5–22.

    Google Scholar 

  11. Akbarzadeh A, Rezaei-sadabady R, Davaran S, Joo SW, Zarghami N. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):1–9.

    Google Scholar 

  12. Ahn H, Park J. Liposomal delivery systems for intestinal lymphatic drug transport. Biomater Res. 2016;20(36):16–21.

    Google Scholar 

  13. Ye T, Wu Y, Shang L, Deng X, Wang S. Improved lymphatic targeting: effect and mechanism of synthetic borneol on lymph node uptake of 7-ethyl-10-hydroxycamptothecin nanoliposomes following subcutaneous administration. Drug Deliv. 2018;25(1):1461–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ahammed V, Narayan R, Paul J, Nayak Y, Roy B, Shavi GV, et al. Development and in vivo evaluation of functionalized ritonavir proliposomes for lymphatic targeting. Life Sci. 2017;183:11–20.

    CAS  PubMed  Google Scholar 

  15. Niu M, Tan Y, Guan P, Hovgaard L, Lu Y, Qi J, et al. Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study. Int J Pharm. 2014;460(1–2):119–30.

    CAS  PubMed  Google Scholar 

  16. Kaur G, Garg T, Rath G, Goyal AK. Archaeosomes: an excellent carrier for drug and cell delivery. Drug Deliv. 2015;23(7):2497–512.

    PubMed  Google Scholar 

  17. Patel GB, Chen W. Archaeosome immunostimulatory vaccine delivery system †. Curr Drug Deliv. 2005;2:407–21.

    CAS  PubMed  Google Scholar 

  18. Moghimipour E, Kargar M, Handali S. Archaeosomes as means of nano-drug delivery. Rev Med Microbiol. 2014;25:40–5.

    Google Scholar 

  19. Deschatelets L, Sprott GD. Safety of archaeosome adjuvants evaluated in a mouse model. J Liposome Res. 2002;12(4):353–72.

    PubMed  Google Scholar 

  20. Li Z, Chen J, Sun W, Xu Y. Investigation of archaeosomes as carriers for oral delivery of peptides. Biochem Biophys Res Commun. 2010;394(2):412–7.

    CAS  PubMed  Google Scholar 

  21. Li Z, Zhang L, Sun W, Ding Q, Hou Y, Xu Y. Archaeosomes with encapsulated antigens for oral vaccine delivery. Vaccine. 2011;29(32):5260–6.

    CAS  PubMed  Google Scholar 

  22. Alex MRA, Chacko AJ, Jose S, Souto EB. Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur J Pharm Sci. 2011;42:11–8.

    Google Scholar 

  23. Kumar S, Narayan R, Ahammed V, Nayak Y, Naha A, Nayak UY. Development of ritonavir solid lipid nanoparticles by Box Behnken design for intestinal lymphatic targeting. J Drug Deliv Sci Technol. 2018;44:181–9.

    CAS  Google Scholar 

  24. Rai S, Paliwal R, Gupta PN, Khatri K, Goyal AK, Vaidya B, et al. Solid lipid nanoparticles (SLNs) as a rising tool in drug delivery science: one step up in nanotechnology. Curr Nanosci. 2008;4:30–44.

    CAS  Google Scholar 

  25. Paliwal R, Rai S, Vaidya B, Khatri K, Goyal AK, Mishra N, et al. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine. 2009;5(2):184–91.

    CAS  PubMed  Google Scholar 

  26. Narendar D, Goverdhan P. Capecitabine lipid nanoparticles for anti-colon cancer activity in 1, 2-dimethylhydrazine induced colon cancer: preparation, cytotoxic, pharmacokinetic and pathological evaluation. Drug Dev Ind Pharm. 2018:1–11.

  27. Desai J, Thakkar H. Darunavir-loaded lipid nanoparticles for targeting to HIV reservoirs. AAPS PharmSciTech. 2018;19(2):648–60.

    CAS  PubMed  Google Scholar 

  28. Makwana V, Jain R, Patel K, Nivsarkar M, Joshi A. Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: elucidation of mechanism of uptake using chylomicron flow blocking approach. Int J Pharm. 2015;495(1):439–46.

    CAS  PubMed  Google Scholar 

  29. Baek J, Cho C. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake. Eur J Pharm Biopharm. 2017;117:132–40.

    CAS  PubMed  Google Scholar 

  30. Vivek R, Jose S. Development, evaluation and targeting of imatinib mesylate loaded solid lipid nanoparticles to the lymphatic system. Int J Pharm Sci Res. 2018;9(6):2359–68.

    CAS  Google Scholar 

  31. Ghassemi S, Haeri A, Shahhosseini S, Dadashzadeh S. Labrasol-enriched nanoliposomal formulation: novel approach to improve oral absorption of water-insoluble drug. Carvedilol AAPS PharmSciTech. 2018;19(7):2961–70.

    CAS  PubMed  Google Scholar 

  32. Jawahar N, Hingarh PK, Arun R, Selvaraj J, Anbarasan A, Sathianarayanan S, et al. Enhanced oral bioavailability of an antipsychotic drug through nanostructured lipid carriers. Int J Biol Macromol. 2018;110:269–75.

    CAS  PubMed  Google Scholar 

  33. Khan S, Shaharyar M, Fazil M, Hassan Q. Tacrolimus-loaded nanostructured lipid carriers for oral delivery—in vivo. Eur J Pharm Biopharm. 2016;109:149–57.

    CAS  PubMed  Google Scholar 

  34. Mishra A, Imam SS, Aqil M, Ahad A, Sultana Y, Ali A. Carvedilol nano lipid carrier: formulation, characterization and in-vivo evaluation. Drug Deliv. 2016;23(4):1486–94.

    CAS  PubMed  Google Scholar 

  35. Wauthoz N, Bastiat G, Moysan E, Cie A, Kondo K, Zandecki M, et al. Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice. Nanomedicine. 2015;11:1237–45.

    CAS  PubMed  Google Scholar 

  36. Li Y, Hu X, Lu X, Liao D, Tang T. Nanoemulsion-based delivery system for enhanced oral bioavailability and caco-2 cell monolayers permeability of berberine hydrochloride. Drug Deliv. 2017;24(1):1868–73. https://doi.org/10.1080/10717544.2017.1410257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Garga B, Katare OP, Beg S, Lohan S, Singh B. Systematic development of solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the oral bioavailability and intestinal lymphatic uptake of lopinavir. Colloids Surf B Biointerfaces. 2016;141:611–22.

    Google Scholar 

  38. Singh G, Pai RS. Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies. Drug Deliv. 2015;22(4):522–30.

    CAS  PubMed  Google Scholar 

  39. Dou Y, Wang T, Huang Y, Ping V, Xie Y, Lin X, et al. Self-nanoemulsifying drug delivery system of bruceine D: a new approach for anti-ulcerative colitis. Int J Nanomedicine. 2018;Volume 13:5887–907.

    Google Scholar 

  40. Nooli M, Chella N, Kulhari H, Shastri NR, Sistla R. Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation, optimization and in vivo evaluation. Drug Dev Ind Pharm. 2017;43(4):611–7.

    CAS  PubMed  Google Scholar 

  41. Zhao B, Gu S, Du Y, Shen M, Liu X, Shen Y. Solid lipid nanoparticles as carriers for oral delivery of hydroxysafflor yellow A. Int J Pharm. 2018;535(1–2):164–71.

    CAS  PubMed  Google Scholar 

  42. Mishra A, Vuddanda PR, Singh S. Intestinal lymphatic delivery of praziquantel by solid lipid nanoparticles: formulation design, in vitro and in vivo studies. J Nanotechnol. 2014;2014:1–12.

    Google Scholar 

  43. Khan S, Baboota S, Ali J, Khan S, Narang RS, Narang JK. Nanostructured lipid carriers: an emerging platform for improving oral bioavailability of lipophilic drugs. Int J Pharm Investig. 2015;5(4):182–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Heurtault B, Saulnier P, Pech B, Proust J, Benoit J. A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharm Res. 2002;19(6):875–80.

    CAS  PubMed  Google Scholar 

  45. Couvreur P, Barratt G, Fattal E, Legrand PVC. Nanocapsule technology: a review. Crit Rev Ther Drug Carrier Syst. 2002;19(2):99–134.

    CAS  PubMed  Google Scholar 

  46. Mehanna M, Motawaa A, Samaha M. Pharmaceutical particulate carriers: lipid-based carriers. Natl J Physiol Pharm Pharmacol. 2012;2(1):10–22.

    CAS  Google Scholar 

  47. Mora-huertas CE, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. Int J Pharm. 2010;385:113–42.

    CAS  PubMed  Google Scholar 

  48. Khoee S, Yaghoobian M. An investigation into the role of surfactants in controlling particle size of polymeric nanocapsules containing penicillin-G in double emulsion. Eur J Med Chem. 2009;44(6):2392–9.

    CAS  PubMed  Google Scholar 

  49. Varshosaz J, Taymouri S, Jahanian-Najafabadi AAA. Efavirenz oral delivery via lipid nanocapsules: formulation, optimisation, and ex-vivo gut permeation study. IET Nanobiotechnol. 2018;12(6):795–806.

    PubMed  PubMed Central  Google Scholar 

  50. Peltier S, Oger J, Couet W, Benoı J. Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules. Pharm Res. 2006;23(6):1243–50.

    CAS  PubMed  Google Scholar 

  51. Ranpise AA, Wagh MP. Lipid-based self-microemulsifying drug delivery system: a novel approach for lipophilic drugs. J Pharm Res. 2018;12(4):560–70.

    CAS  Google Scholar 

  52. Wu W, Wang Y, Que L. Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur J Pharm Biopharm. 2006;63:288–94.

    CAS  PubMed  Google Scholar 

  53. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004;58:173–82.

    PubMed  Google Scholar 

  54. Priyanka G, Divyesh S. Self-micro-emulsifying drug delivery system to enhance the solubility of the hydrophobic drugs. Curr Trends Biomed Eng Biosci. 2018;13(4):001–6.

    Google Scholar 

  55. Pokale R, Bandivadekar M. Self micro-emulsifying drug delivery system for lymphatic uptake of darunavir. J Drug Discov Dev Deliv. 2016;3(2):1–7.

    Google Scholar 

  56. Zhang P, Liu Y, Feng N, Xu J. Preparation and evaluation of self-microemulsifying drug delivery system of oridonin. Int J Pharm. 2008;355:269–76.

    CAS  PubMed  Google Scholar 

  57. Shen H, Zhong M. Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin. J Pharm Pharmacol. 2006;58:1183–91.

    CAS  PubMed  Google Scholar 

  58. Cui J, Yu B, Zhao Y, Zhu W, Li H, Lou H, et al. Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. Int J Pharm. 2009;371:148–55.

    CAS  PubMed  Google Scholar 

  59. Debnath S, Kumar GV. Nanoemulsion—a method to improve the solubility of lipophilic drugs. Pharmanest. 2011;2:72–83.

    Google Scholar 

  60. Sureshkumar R, Gowthamarajan K, Bhavani P. Nanoemulsion for lymphatic absorption: investigation of fenofibrate nanoemulsion system for lymphatic uptake. Int J ChemTech Res. 2015;7(2):832–41.

    Google Scholar 

  61. Mandal S, Mandal SS, Sawant KK. Design and development of microemulsion drug delivery system of atorvastatin and study its intestinal permeability in rats. Int J Drug Deliv. 2010;2:69–75.

    CAS  Google Scholar 

  62. Hallan SS, Kaur P, Kaur V, Mishra N, Vaidya B. Lipid polymer hybrid as emerging tool in nanocarriers for oral drug delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):334–49.

    CAS  PubMed  Google Scholar 

  63. Ren T, Wang Q, Xu Y, Cong L, Gou J, Tao X, et al. Enhanced oral absorption and anticancer efficacy of cabazitaxel by overcoming intestinal mucus and epithelium barriers using surface polyethylene oxide (PEO) decorated positively charged polymer-lipid hybrid nanoparticles. J Control Release. 2018;269:423–38.

    CAS  PubMed  Google Scholar 

  64. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm. 1998;172(1–2):33–70.

    CAS  Google Scholar 

  65. Karim KM, Sattwa A. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;1(4):374–80.

    CAS  Google Scholar 

  66. Jain CP, Vyas SPDV. Niosomal system for delivery of rifampicin to lymphatics. Indian J Pharm Sci. 2006;68(5):575–8.

    CAS  Google Scholar 

  67. Jain CPVS. Lymphatic delivery of niosome encapsulated methotrexate. Pharmazie. 1995;50(5):367–8.

    CAS  PubMed  Google Scholar 

  68. Bakhtiari H. Niosomal carriers enhance oral bioavailability of carvedilol: effects of bile salt-enriched vesicles and carrier surface charge. Int J Nanomedicine. 2015;10:4797–813.

    Google Scholar 

  69. Hingorani L, Ebersole B. Stable solid lipid particle composition for improved bioavailability of lipophilic compounds for age-related diseases. US; US20170333362A1, 2017.

  70. Zhiqiang G, Weiran H, Xinying D. Oral thymosin alpha-1 solid lipid nanoparticle absorption preparation and preparing method thereof. China; CN103405752A, 2013.

  71. Yongzhong D, Tour S, Fuqiang H, Yuan H. Vinorelbine solid lipid nano granule, freeze drying formulated product and method of preparing the same. China; CN101129375B, 2007.

  72. Chuhong, Hao W, Jinhong G. Gemcitabine solid lipid nanospheres, preparation method thereof and use thereof. China; CN101926779A, 2010.

  73. Rongping Y, Yunhong W, Yao J, Weiwei Q, Nan L, Xiangxiang G, et al. Indirubin one kind SMEDDS its preparation method. China; CN104055733B, 2014.

  74. Hongtao S, Zhihong L, Xiongwei H, Jing Z, Xu W. Sirolimus self-microemulsion preparation and preparation method thereof. China; CN105640886A, 2016.

  75. Jin S, Zhonggui H, Xinxia R, Yinghua S, Xueqin Z, Cong L. Lacidipine self-microemulsifying soft capsules and preparation method thereof. China; CN102008471B, 2010.

  76. Murty Ram B, Murty Santosh B. An improved oral dosage form of tetrahydrocannabinol and a method of avoiding and/or suppressing hepatic first-pass metabolism via targeted chylomicron/lipoprotein delivery. US; WO2012033478A1, 2012.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suresh P. Vyas.

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

Vishwakarma, N., Jain, A., Sharma, R. et al. Lipid-Based Nanocarriers for Lymphatic Transportation. AAPS PharmSciTech 20, 83 (2019). https://doi.org/10.1208/s12249-019-1293-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-019-1293-3

KEY WORDS

Navigation