Fabrication, optimization, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers for improved anticancer activity

Abstract

Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is the leading cancer killer in both men and women in every Ethnic Group. A major problem associated with chemotherapies against their lung cancer is the lack of selective toxicity, which results in a narrow therapeutic index thereby compromising clinical prognosis. To circumvent these challenges, the present investigation sought to develop a docetaxel-loaded nanostructured lipid carrier system (DTX-NLCS) for the treatment of lung cancer. A 3-factor/3-level Box-Behnken Design was applied to systematically optimize the DTX-NLCS parameters. The amount of drug, emulsifier concentration, and homogenization speed was selected as independent variables, while the particle size and % entrapment efficiency (%EE) were selected as dependent variables. The optimized batch parameters were 29.81 mg drug, 19.97% w/w emulsifier, and 13 200 (rpm) speed of homogenization with a mean particle size of 154.1 ± 3.13 nm and a mean %EE of 86.12 ± 3.48%. The in vitro lipolysis experiments revealed that the optimized DTX-NLCs were stabilized by 10% w/w PEG 4000 mono-stearate and exhibited an anti-lipolytic effect. Furthermore, the in vitro gastrointestinal stability studies (at pH-1.2, pH-4.5, pH-6.8, and pH-7.4) revealed that the optimized developed system could withstand various GI tract media. The in vitro dissolution studies depicted a pH-independent controlled-release consistent with the Weibull model. In vitro cytotoxicity studies using NCI-H460 cell lines further revealed that there was a reduction in IC₅₀ values in the DTX-NLCS treated cells as compared to those treated with the pure drug, indicating an improved efficiency for the developed system.

Graphical Abstract

Keywords:

• Lipid nanoparticles
• Box-Behnken design
• lipolysis
• oral delivery
• lymphatic delivery

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are highly thankful to Nirma University, Ahmedabad, India for providing financial assistance in form of Major Research Project [Grant No.: NU/Ph.D./Major Res Pro/IP/16–17/669] and for providing necessary facilities to carry out the research work. The authors are also thankful to Department of Science and Technology (DST), Fund for Improvement of S&T Infrastructure (FIST) [Grant No.: SR/FST/LSI-607/2014], Government of India for providing the necessary funding to establish equipment facility.