ABSTRACT
The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment.
Subject(s)
Doxorubicin/chemistry , Nanostructures/chemistry , Oleic Acid/chemistry , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic InteractionsABSTRACT
The objective of the present work was to investigate the effects of the mixture of nonionic/ionic surfactants on nanostructured lipid carriers (NLCs). Nonionic surfactant (polyethylene-poly(propylene glycol), Pluronic F68) and ionic surfactant (octenylsuccinic acid modified gum arabic, GA-OSA) were chosen as emulsifier for NLCs. The NLCs systems, which were composed of lipid matrix, modified 4-dedimethylaminosancycline (CMT-8), and various emulsifier agents, were characterized with dynamic light scattering (DLS), high performance liquid chromatography (HPLC), transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), in vitro release, and phagocytosis assay. This mixture of nonionic/ionic surfactants showed significant effects on physical properties including particle size, polydispersity index (PDI), entrapment efficiency, and particle morphology. Compared with single stabilizer, this mixed nonionic/ionic surfactant system provided NLCs with better drug carrier properties including prolonged release profile and low phagocytosis by phagocyte. We expect that these explorations can provide a new strategy for the development of lipid nanoparticles as drug delivery.
