title: Development and in vitro cytotoxic evaluation of parenteral docetaxel lipid nanoemulsions for application in cancer treatment.
abstract: The aim of the present study was to develop stable lipid nanoemulsions (LNEs) for delivery of docetaxel for treatment of cancer. The LNEs of docetaxel were prepared by using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The influence of formulation variables such as change in proportion of charge inducers, that is, oleic acid (negative) and stearyl amine (positive), was studied. Stable LNEs of docetaxel having the mean size range of 190-230 nm and zeta potential of -19.2 to -31 mV in the case of oleic acid emulsions and 49.5 to 50.5 mV in the case of stearyl amine emulsions were developed. There was considerable increase in zeta potential value on increasing concentration of oleic acid, whereas no such effect was observed on increasing stearyl amine concentration. During in vitro studies the cumulative amount of docetaxel released from LNE (control emulsion), LNE-O1, LNE-O2, LNE-O3, LNE-S1, LNE-S2, and LNE-S3 was determined. The results indicated that there was no significant effect in varying the concentration of charge inducers on size and in vitro cumulative release of prepared LNEs at 12 h. The optimized formulations were identified as LNE-O3 and LNE-S3 based on relative stabilities during centrifugal stress, dilution stress, and in storage at room temperature. The total drug content and entrapment efficiency of LNE-O3 were found to be 0.96 ± 0.02 mg/mL and 96.35 ± 1.21%, respectively, whereas for LNE-S3 the total drug content and entrapment efficiency were 0.97 ± 0.01 mg/mL and 97.07 ± 0.82%, respectively. During in vitro studies on cancer cell lines both of the optimized formulations, LNE-O3 and LNE-S3, showed similar values of IC50 (half maximal inhibitory concentration) in comparison to docetaxel solution. Based on this, it was concluded that the optimized LNEs were efficacious for the delivery of docetaxel and could act as alternative delivery systems to overcome the poor solubility, hydrolytic instability, and drug-induced and vehicle-related side effects of docetaxel.
authors.affiliation: Nanotechnology Research Lab, Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India, 506009.
authors.forename: Isnepally
authors.initials: I
authors.lastname: Venkateshwarlu
authors.forename: Kandadi
authors.initials: K
authors.lastname: Prabhakar
authors.forename: Mubarak
authors.initials: M
authors.lastname: Ali
authors.forename: Veerabrahma
authors.initials: V
authors.lastname: Kishan
mesh_terms: D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D006801:Humans; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility
chemical_list: D004655:Emulsions