Co-Delivery of siRNA and Docetaxel to Cancer Cells by NLC for Therapy
Behiye Şenel1, Ebru Başaran2, Evrim Akyıl2
1Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Anadolu University, 26470 Eskisehir, Türkiye.
Abstract:
The present study aims to develop a delivery system that can carry small interference RNA (siRNA) with small-molecule chemotherapeutic drugs, which can be used in cancer treatment. The drug delivery system combines the advantages of a therapeutic agent with two different mechanisms to ensure that it is used efficiently for cancer therapy. In this study, a nanostructured lipid carrier system was prepared, Docetaxel was loaded to these systems, and the Eph siRNA was adsorbed to the outer surface. In addition, DOTAP was added to the lipophilic phase to load a positive charge on the lipidic structure for interaction with the cells. Moreover, characterization, cytotoxicity, and transfection procedures were performed on the whole system. This candidate system was also compared to Taxotere, which is the first approved Docetaxel-containing drug on the market. Given the results, it was determined that the particle size of NLC-DTX was 165.3 ± 3.5 nm, the ζ potential value was 38.2 ± 1.7 mV, and the PDI was 0.187 ± 0.024. Entrapment efficacy of nanoparticles was found to be 92.89 ± 0.21%. It was determined that the lipidic system prepared in vitro release analyses were able to provide sustained release and exhibit cytotoxicity, even at doses lower than the dose used for Taxotere. The formulations prepared had a higher level of effect on cells when compared with pure DTX and Taxotere, but they also exhibited time-dependent cytotoxicity. It was also observed that the use of Eph siRNA together with the chemotherapeutic agent via formulation also contributed to this cell death. The results of the present study indicate that there is a promising carrier system in order to deliver hydrophilic nucleic acids, such as siRNA, together with lipophilic drugs in cancer treatment.
Insights
This study developed a novel nanostructured lipid carrier system for co-delivery of small interference RNA (siRNA) and Docetaxel chemotherapy, showing enhanced cancer cell death and sustained drug release compared to existing treatments.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Oncology
Background:
- Effective cancer treatment requires efficient delivery of both chemotherapeutics and nucleic acid-based therapies.
- Existing drug delivery systems often struggle with co-delivering lipophilic drugs and hydrophilic nucleic acids like siRNA.
- Developing advanced carriers is crucial for improving therapeutic efficacy and overcoming drug resistance.
Purpose of the Study:
- To develop and characterize a novel nanostructured lipid carrier (NLC) system for co-delivering Docetaxel (DTX) and Eph siRNA for cancer therapy.
- To evaluate the physicochemical properties, in vitro release kinetics, cytotoxicity, and transfection efficiency of the developed NLC system.
- To compare the efficacy of the NLC-DTX/siRNA system against free DTX and the commercial drug Taxotere.
Main Methods:
- Preparation of NLCs loaded with Docetaxel and surface-adsorbed Eph siRNA, incorporating DOTAP for positive charge.
- Physicochemical characterization including particle size, zeta potential, polydispersity index (PDI), and entrapment efficiency.
- In vitro drug release studies, cytotoxicity assays, and transfection efficiency evaluations on cancer cells.
- Comparative analysis with free Docetaxel and Taxotere.
Main Results:
- The NLC-DTX/siRNA system exhibited optimal particle size (165.3 nm), positive zeta potential (38.2 mV), and low PDI (0.187), with high DTX entrapment efficacy (92.89%).
- The NLC system demonstrated sustained in vitro release of Docetaxel and significant cytotoxicity, even at lower doses than Taxotere.
- Co-delivery of Eph siRNA and Docetaxel via the NLC formulation resulted in enhanced cancer cell death compared to individual components or Taxotere, showing time-dependent cytotoxicity.
Conclusions:
- The developed nanostructured lipid carrier system is a promising platform for the co-delivery of lipophilic drugs and hydrophilic nucleic acids like siRNA in cancer treatment.
- This dual-mechanism delivery system enhances therapeutic efficacy and exhibits potent, time-dependent cytotoxicity against cancer cells.
- The NLC-DTX/siRNA formulation represents a significant advancement over current chemotherapy delivery methods, offering improved treatment potential.
