Development of pimozide spray dried lipid nanoparticles with enhanced targeting of non-small cell lung cancer

This study aims to develop and evaluate the pimozide-loaded lipid nanoparticles (LNPs) designed for the targeted treatment of non-small cell lung cancer (NSCLC). Employing the microemulsion technique, three distinct types of LNPs were synthesized: solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and liquid lipid carriers (LLC). These formulations were optimized in order to transform them into fine powders through spray drying. An assessment of their encapsulation efficiency (EE%), particle size, moisture sorption, surface morphology, and anti-proliferative activity against A549 lung cancer cells were evaluated. NLC formulations exhibited the highest EE% at approximately 96 % ± 2.1 %, attributed to the inclusion of oleic acid, which disrupted the lipid matrix's crystalline structure to enhance drug encapsulation. In contrast, SLN formulations demonstrated the lowest EE%, with values barely exceeding 70 % ± 2.5 %, highlighting the limitations of their solid lipid content. The spray drying process significantly altered the particle sizes, transitioning them from nano to microscale and resulting in a modest decline in EE% across all LNP types. Further, DVS analyses highlighted the moisture sorption capabilities of the LNPs, showing diverse trends among the formulations. LLCs demonstrated the highest sorption capacity, suggesting a highly porous structure. FTIR spectroscopic analysis revealed specific interactions between the drug and lipid matrix, indicating successful encapsulation. Raman spectroscopy further confirmed the uniform distribution of pimozide and excipients within the LNPs and highlighted how oleic acid and PEG-400 co-localize, crucial for boosting drug loading capabilities. X-ray powder diffraction (XRPD) analysis showed varying degrees of crystallinity across the formulations, with LLCs exhibiting the most amorphous nature followed by NLCs and then SLNs. Surface morphology studies through SEM analysis showed the transformation from nanoparticles to microparticles post spray drying, with distinct textural differences among the formulations. The anti-proliferative activity against A549 cells identified NLC 4, NLC 5, and LLC 5 as particularly effective, with IC50 values notably lower than that of free PMZ, highlighting improved therapeutic potential. Drug release studies revealed a biphasic release pattern for the promising formulations, offering sustained drug availability, crucial for effective NSCLC treatment.