Abstract
One of the most favored features of using nanoparticulate delivery systems such as solid lipid nanoparticles (SLNs) is their capability to encapsulate multi-agents of different chemical structures to achieve simultaneous delivery to the site of action. The present work has been carried out to elaborate a convenient methodology for the loading of the drug combination efficiently and with high drug content. Thus, two representatives of the naturally occurring flavonoids (FLs) with a broad spectrum of biological functions, i.e., fisetin (FIS) or myricetin (MYR), along with the indocyanine-type photosensitizer IR-780 were co-loaded in the cetyl palmitate (CP) matrix of the phosphatidylcholine-based solid lipid nanoparticles (SLNs) by means of the high pressure homogenization method (HPH). The HPH process – optimized in regard to different ratios of combination drugs, particle components content as well as variable parameters as pressure and number of homogenization cycles – provided physically stable and fairly monodisperse FL+IR-780-loaded SLN dispersions (with polydispersity indices below 0.3). The sizes of the studied nanosystems along with the size distribution were determined by dynamic light scattering (DLS), while shape and morphology – by atomic force microscopy (AFM). The physical state of the studied co-loaded SLNs was characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TG-DTA). Both FLs and IR-780 preserved their structural state and were thoroughly dispersed in the CP-matrix during the HPH procedure. Our synthetic methodology enabled to perform remote loading of two drugs (FIS or MYR and IR-780) in the SLN – type nanocarriers having desirable chemical and colloidal stability, making them useful for therapeutic and diagnostic applications or combination therapies.
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