Docetaxel-loaded borage seed oil nanoemulsion with improved antitumor activity for solid tumor treatment: Formulation development, in vitro, in silico and in vivo evaluation

In the present work, docetaxel-nanoemulsion (DTX-NE) was developed with the aim to improve its therapeutic activity while reducing the side-effects by targeted delivery approach. The unique approach about the developed formulation was use of borage seed oil as the oil phase which has abundant gamma-linolenic acid (GLA) in it and has been previously reported for its anticancer activity. DTX was solubilized in Borage oil and the system was emulsified using Phospholipid (Lipoid E-80). The nanoemulsion was developed by high shear homogenization and ultrasonication. Systematic optimization of critical factors was carried out using Box-Behnken design. The optimized nanoemulsion showed particle size (180.2 & PLUSMN; 4.5 nm), zeta potential (-33.7 & PLUSMN; 1.9 mV) and PDI (0.178 & PLUSMN; 0.01) within the desired limits. The drug entrapment efficiency was found to be 96.41 & PLUSMN; 4.7% while drug loading was found to be 12.87 & PLUSMN; 1.3%. Further, FTIR, DSC and XRD analysis revealed compatibility of the drug with the excipients in addition to complete drug solubilization and entrapment. Further, in vitro release study performed in PBS (pH 7.4) indicated a biphasic profile while release kinetic evaluation showed best fitting as per Korsemeyer-Peppas model with drug release through Fickian diffusion mechanism. In silico docking performed of DTX and GLA suggested excellent binding with microtubule subunit with the binding affinity of-6.4 kcal/mol and-5.7 kcal/mol, respectively. In vivo pharmacokinetic studies in Albino Wistar rats indicated significant improvement in AUC (3.9-folds), t1/2 (2.0-folds) and MRT (4.0-folds) from DTX-NE vis-`a-vis the plain drug, respectively. Furthermore, antitumor efficacy of DTX-NE showed significant reduction in the tumor growth (3.17-times) than the free drug and marketed formulation (Taxotere (R)).

Automated summary

In this study, a novel docetaxel-nanoemulsion was developed to improve therapeutic effectiveness and reduce side effects through targeted delivery. The optimized nanoemulsion demonstrated excellent characteristics in terms of drug encapsulation, drug release kinetics, and in vivo pharmacokinetics.