Optimisation of Sub-30 nm Solid Lipid Nanoparticles Loaded With Docetaxel Produced by the Cold-Burst Method: A Particle Size Optimisation Study.

INTRODUCTION

The cold-burst method presents a novel, energy-efficient, and cost-effective approach for solid lipid nanoparticle (SLN) production compared to traditional methods. It involves simple heating and cooling cycles that can create SLNs below 30 nm in size. Given the limitations of conventional docetaxel (DTX) delivery in cancer therapy, SLNs offer a promising solution for improved bioavailability and reduced toxicity. The achievement of sub-30 nm SLNs is particularly significant, as this size range is known to enhance passive tumour targeting via the enhanced permeability and retention (EPR) effect, promote deeper distribution into solid tumours, and improve cellular uptake. This study aimed to optimise the particle size of DTX-loaded SLNs produced via the cold-burst method.

METHOD

Formulations utilised Compritol 888 ATO (888) and Precirol ATO 5 (ATO5) as lipid components, stabilised by water-soluble (Tween20, BrijS20) and oil-soluble (monoolein) surfactants. A total of 25 SLN formulations were created by systematically varying parameters including type of lipid, type of water-soluble surfactant, DTX concentration (0-5 wt%, equating to 0-5 mg), total surfactant concentration (2-4 wt%), water-soluble surfactant ratio, and number of heating and cooling cycles. Particle size (mean D50) was determined by dynamic light scattering (DLS) using a Malvern Zetasizer Nano ZS series (Malvern Panalytical, Shanghai, China). Statistical comparisons of mean D50 values were performed using one-way analysis of variance (ANOVA) followed by Tukey's honestly significant difference (HSD) post hoc analysis.

RESULTS

This study's results consistently demonstrated the successful formation of <30 nm DTX-loaded SLNs for both lipids. Drug loading of up to 5 wt% DTX showed no significant difference in particle size when compared to no drug loading. A significant decrease in particle size was observed with increasing total surfactant concentration (2-4 wt%). Both water-soluble surfactants used in this study, Tween20 and BrijS20, facilitated cold bursting and the creation of sub-30 nm SLNs, with BrijS20 yielding significantly smaller nanoparticles across both lipid types. The most pronounced size reduction for 888 SLNs occurred within the first heating and cooling cycle.

CONCLUSION

These findings highlight the potential of cold-burst-derived sub-30 nm SLNs as an optimised platform. Our work demonstrates the successful optimisation of particle size for DTX-loaded SLNs, laying a foundation for future comprehensive studies towards enhanced DTX delivery and more effective cancer therapeutics. However, the absence of drug loading quantification, in vitro drug release data, and cellular performance assessments limits the conclusions regarding the therapeutic efficacy of these SLNs.