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