AAPS PharmSciTech

, 20:87 | Cite as

Paclitaxel-loaded Nanolipidic Carriers with Improved Oral Bioavailability and Anticancer Activity against Human Liver Carcinoma

  • Harshita
  • Md Abul BarkatEmail author
  • Md Rizwanullah
  • Sarwar BegEmail author
  • Faheem Hyder Pottoo
  • Sahabjada Siddiqui
  • Farhan J. AhmadEmail author
Research Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery


The poorly water-soluble chemotherapeutic agents, paclitaxel (PTX), exhibit serious clinical side effects upon oral administration due to poor aqueous solubility and a high degree of toxic effects due to non-specific distribution to healthy tissues. In our efforts, we formulated biocompatible dietary lipid-based nanostructured lipidic carriers (NLCs) to enhance the oral bioavailability of PTX for treatment of the liver cancer. A three-factor, three-level Box–Behnken design was employed for formulation and optimization of PTX-loaded NLC formulations. PTX-loaded NLC formulation prepared by melt-emulsification in which glyceryl monostearate (GMS) was used as solid lipid and soybean oil as liquid lipid, while poloxamer 188 and Tween 80 (1:1) incorporated as a surfactant. In vitro drug release investigation was executed by dialysis bag approach, which indicated initial burst effect with > 60% drug release within a 4-h time period. Moreover, PTX-NLCs indicated high entrapment (86.48%) and drug loading efficiency (16.54%). In vitro cytotoxicity study of PTX-NLCs performed on HepG2 cell line by MTT assay indicated that PTX-NLCs exhibited comparatively higher cytotoxicity than commercial formulation (Intaxel®). IC50 values of PTX-NLCs and Intaxel® after 24-h exposure were found to be 4.19 μM and 11.2 μM. In vivo pharmacokinetic study in Wistar rats also indicated nearly 6.8-fold improvement in AUC and Cmax of the drug from the PTX-NLCs over the PTX suspension. In a nutshell, the observed results construed significant enhancement in the biopharmaceutical attributes of PTX-NLCs as a potential therapy for the management of human liver carcinoma.


nanostructured lipid carriers paclitaxel Box–Behnken design optimization melt-emulsification technique human liver carcinoma 



The authors are grateful to Gattefosse for providing gift samples of oils and co-surfactants, and Fresenius Kabi India Pvt. Ltd. for PTX. The authors also acknowledge the kind help from Dr. M. Arshad, Deptt. Zoology, Lucknow University, India, for in vitro cell culture studies.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interests.


  1. 1.
    Best J, Schotten C, Theysohn JM, Wetter A, Müller S, Radünz S, et al. Novel implications in the treatment of hepatocellular carcinoma. Ann Gastroenterol. 2017;30(1):23–32.PubMedGoogle Scholar
  2. 2.
    Li S, Zheng L. Effect of combined treatment using wilfortrine and paclitaxel in liver cancer and related mechanism. Med Sci Monit. 2016;22:1109–14.CrossRefGoogle Scholar
  3. 3.
    Soni K, Rizwanullah M, Kohli K. Development and optimization of sulforaphane-loaded nanostructured lipid carriers by the Box-Behnken design for improved oral efficacy against cancer: in vitro, ex vivo and in vivo assessments. Artif Cells Nanomed Biotechnol. 2017:1–17.
  4. 4.
    Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–48.CrossRefGoogle Scholar
  5. 5.
    Yang XY, Li YX, Li M, Zhang L, Feng LX, Zhang N. Hyaluronic acid coated nanostructured lipid carriers for targeting paclitaxel to cancer. Cancer Lett. 2013;334(2):338–45.CrossRefGoogle Scholar
  6. 6.
    Sandhu PS, Beg S, Mehta F, Singh B, Trivedi P. Novel dietary lipid-based selfnanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance. Expert Opin Drug Deliv. 2013;12(11):1809–22.CrossRefGoogle Scholar
  7. 7.
    Rivkin I, Cohen K, Koffler J, Melikhov D, Peer D, Margalit R. Paclitaxel clusters coated with hyaluronan as selective tumor-targeted nanovectors. Biomaterials. 2010;31(27):7106–14.CrossRefGoogle Scholar
  8. 8.
    Akhter MH, Rizwanullah M, Ahmad J, Ahsan MJ, Mujtaba MA, Amin S. Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics. Artif Cells Nanomed Biotechnol. 2018;46(5):873–84.CrossRefGoogle Scholar
  9. 9.
    Ahmad J, Akhter S, Rizwanullah M, Amin S, Rahman M, Ahmad MZ, et al. Nanotechnology-based inhalation treatments for lung cancer: state of the art. Nanotechnol Sci Appl. 2015;8:55–66.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Beg S, Saini S, Bandopadhyay S, Katare OP, Singh B. QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of olmesartan medoxomil employing multivariate statistical techniques. Drug Dev Ind Pharm. 2018;44(3):407–20.CrossRefGoogle Scholar
  11. 11.
    Barkat MA, Harshita, Ahmad J, Khan MA, Beg S, Ahmad FJ. Insights into the targeting potential of Thymoquinone for therapeutic intervention against triple-negative. Breast Cancer Curr Drug Targets 2018;19(1):70–80.Google Scholar
  12. 12.
    Hussain A, Wais M, Singh SK, Samad A, Nazish I, Beg S. Nanostructured lipidic carriers for oral bioavailability enhancement. Recent Pat Nanomed. 2015;5(2):78–86.CrossRefGoogle Scholar
  13. 13.
    Granja A, Vieira AC, Chaves LL, Nunes C, Neves AR, Pinheiro M, et al. Folate-targeted nanostructured lipid carriers for enhanced oral delivery of epigallocatechin-3-gallate. Food Chem. 2017;237:803–10.CrossRefGoogle Scholar
  14. 14.
    Gao X, Zhang J, Xu Q, Huang Z, Wang Y, Shen Q. Hyaluronic acid-coated cationic nanostructured lipid carriers for oral vincristine sulfate delivery. Drug Dev Ind Pharm. 2017;43(4):661–7.CrossRefGoogle Scholar
  15. 15.
    Sun B, Luo C, Li L, Wang M, Du Y, Di D, et al. Core-matched encapsulation of an oleate prodrug into nanostructured lipid carriers with high drug loading capability to facilitate the oral delivery of docetaxel. Colloids Surf B Biointerfaces. 2016;143:47–55.CrossRefGoogle Scholar
  16. 16.
    Aditya NP, Shim M, Lee I, Lee Y, Im MH, Ko S. Curcumin and genistein coloaded nanostructured lipid carriers: in vitro digestion and antiprostate cancer activity. J Agric Food Chem. 2013;61(8):1878–83.CrossRefGoogle Scholar
  17. 17.
    Beg S, Rahman M, Kohli K. Quality-by-design approach as a systematic tool for the development of nanopharmaceutical products. Drug Discov Today. 2018.Google Scholar
  18. 18.
    Beg S, Rahman M, Rahman Z, Akhter S. Perspectives of quality by design approach in nanomedicines development. Curr Nanomed. 2017;7:191–7.CrossRefGoogle Scholar
  19. 19.
    Singh B, Raza K, Beg S. Developing “optimized” drug products employing “designed” experiments. Chem Ind Digest. 2013;23:70–6.Google Scholar
  20. 20.
    Singh B, Beg S. Attaining product development excellence and federal compliance employing quality by design (QbD) paradigms. Pharma Rev. 2015;13(9):35–44.Google Scholar
  21. 21.
    Singh B, Beg S. Product development excellence and federal compliance via QbD. Chronicle Pharmabiz. 2014;15(10):30–5.Google Scholar
  22. 22.
    Singh B, Beg S. Quality by design in product development life cycle. Chronicle Pharmabiz. 2013;22:72–9.Google Scholar
  23. 23.
    Rizwanullah M, Amin S, Ahmad J. Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers. J Drug Target. 2017;25(1):58–74.CrossRefGoogle Scholar
  24. 24.
    Qidwai A, Khan S, Md S, Fazil M, Baboota S, Narang JK, et al. Nanostructured lipid carrier in photodynamic therapy for the treatment of basal-cell carcinoma. Drug Deliv. 2016;23(4):1476–85.CrossRefGoogle Scholar
  25. 25.
    Xu W, Lee MK. Development and evaluation of lipid nanoparticles for paclitaxel delivery: a comparison between solid lipid nanoparticles and nanostructured lipid carriers. J Pharm Investig. 2015;45(7):675–80.CrossRefGoogle Scholar
  26. 26.
    Barkat MA, Harshita AI, Ali R, Singh SP, Pottoo FH, et al. Nanosuspension-based aloe vera gel of silver sulfadiazine with improved wound healing activity. AAPS PharmSciTech. 2017;18(8):3274–85.CrossRefGoogle Scholar
  27. 27.
    Ahamad MS, Siddiqui S, Jafri A, Ahmad S, Afzal M, Arshad M. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest. PLoS One. 2014;9(10):e110003.CrossRefGoogle Scholar
  28. 28.
    Siddiqui S, Ahmad E, Gupta M, Rawat V, Shivnath N, Banerjee M, et al. Cissus quadrangularis Linn exerts dose-dependent biphasic effects: osteogenic and anti-proliferative, through modulating ROS, cell cycle and Runx2 gene expression in primary rat osteoblasts. Cell Prolif. 2015;48:443–54.CrossRefGoogle Scholar
  29. 29.
    Ahmad J, Mir SR, Kohli K, Chuttani K, Mishra AK, Panda AK, et al. Solid-nanoemulsion preconcentrate for oral delivery of paclitaxel: formulation design, biodistribution, and γ-scintigraphy imaging. Biomed Res Int. 2014;2014:984756.CrossRefGoogle Scholar
  30. 30.
    Tan SW, Billa N, Roberts CR, Burley JC. Surfactant effects on the physical characteristics of amphotericin-B containing nanostructured lipid carriers. Colloids Surf A Physicochem Eng Asp. 2010;372(1–3):73–9.CrossRefGoogle Scholar
  31. 31.
    Liu J, Gong T, Wang C, Zhong Z, Zhang Z. Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization. Int J Pharm. 2007;340(1–2):153–62.CrossRefGoogle Scholar
  32. 32.
    Rahman Z, Zidan AS, Khan MA. Non-destructive methods of characterization of risperidone solid lipid nanoparticles. Eur J Pharm Biopharm. 2010;76(1):127–37.CrossRefGoogle Scholar
  33. 33.
    Mishra A, Imam SS, Aqil M, Ahad A, Sultana Y, Ameeduzzafar, et al. Carvedilolnano lipid carriers: formulation, characterization and in-vivo evaluation. Drug Deliv. 2016;23(4):1486–94.CrossRefGoogle Scholar
  34. 34.
    Moghddam SM, Ahad A, Aqil M, Imam SS, Sultana Y. Optimization of nanostructured lipid carriers for topical delivery of nimesulide using Box-Behnken design approach. Artif Cells Nanomed Biotechnol. 2017;45(3):617–24.CrossRefGoogle Scholar
  35. 35.
    Alam S, Aslam M, Khan A, Imam SS, Aqil M, Sultana Y, et al. Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail. Drug Deliv. 2016;23(2):601–9.CrossRefGoogle Scholar
  36. 36.
    Khan A, Imam SS, Aqil M, Ahad A, Sultana Y, Ali A, et al. Brain targeting of temozolomide via the intranasal route using lipid-based nanoparticles: brain pharmacokinetic and scintigraphic analyses. Mol Pharm. 2016;13(11):3773–82.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics, School of Medical & Allied SciencesK.R. Mangalam UniversitySohnaIndia
  2. 2.Department of Pharmaceutics, Faculty of PharmacyIntegral UniversityLucknowIndia
  3. 3.Nanomedicine Research Lab, Department of PharmaceuticsSchool of Pharmaceutical Education and ResearchNew DelhiIndia
  4. 4.Formulation Research Lab, Department of PharmaceuticsSchool of Pharmaceutical Education and ResearchNew DelhiIndia
  5. 5.Department of Pharmacology, College of Clinical PharmacyImam Abdulrahman Bin Faisal University (Formerly University of Dammam)DammamSaudi Arabia
  6. 6.Department of Biotechnology, Era’s Lucknow Medical College & HospitalEra UniversityLucknowIndia

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