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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
  • 29 Downloads
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery

Abstract

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.

KEY WORDS

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

Notes

Acknowledgments

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.

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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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