Formulation Optimization of Pravastatin Loaded Long-circulating Liposomes Using a Design of Experiments

Pravastatin (PRAV) is a hydrophilic statin which has been reported to have antiangiogenic and pro-apoptotic effects. However, the beneficial effects of statins on tumour growth are obtained at high doses, the systemic administration of those doses being associated with severe toxicity. Thus, site-specific delivery with liposomal systems may be a novel approach in order to enrich its therapeutic effects, while reducing the overall doses required. The objective of this study was to optimize the formulation of PRAV-loaded long circulating liposomes (LCL-PRAV) by using a D-optimal experimental design. The influence of seven formulation and process factors i.e. phospholipids molar concentration (mM), the molar ratio of phospholipids to cholesterol, the PRAV molar concentration (mM), the hydration temperature (°C), the extrusion temperature (°C), the rotation speed at the formation of the lipid film (rot/min) and the rotation speed at the hydration of the film (rot/min) was studied on PRAV liposomal concentration, the encapsulation efficiency (EE %), liposomal size and the Polydispersity Index (PDI). The desired characteristics of LCL-PRAV are the relatively high drug encapsulation efficiency (> 45%), the low and predictable variation in the drug encapsulation efficiency, the particle size range of 180 200 nm and the low PDI value (< 0.100). The optimized formulation had liposomal PRAV concentration of 6128 ± 237 μg/mL, an encapsulation efficiency of 47 ± 13%, 192.3 ± 5 nm size and a PDI of 0,098 ± 0.006. The overall results showed that PRAV can be successfully incorporated into long-circulating liposomes.