Abstract. The purpose of this research was to formulate nanostructured lipid carriers (NLC) for the parenteral delivery of an anticancer drug, all-trans retinoic acid (ATRA). The ATRA was incorporated into NLC by the de novo emulsification method. The effect of the formulation factor, i.e., type and oil ratio, initial ATRA concentration on physicochemical properties was determined. The anticancer efficacy of ATRA-loaded NLC on HL-60 and HepG2 cells was also studied. NLC was formulated using a blend of solid lipids (cetyl palmitate) and liquid lipids (soybean oil (S), medium-chain triglyceride (M), S/oleic acid (O; 3:1) and M/O (3:1)) at a weight ratio of 1:1. ATRA-loaded NLC had an average size of less than 200 nm (141.80 to 172.95 nm) with a narrow PDI and negative zeta potential that was within an acceptable range for intravenous injection. The results indicated that oleic acid enhanced the ATRAloading capacity of NLC. In vitro ATRA release was only approximately 4.06% to 4.34% for 48 h, and no significant difference in ATRA release rate from all NLC formulations in accordance with the composition of the oil phase. Moreover, no burst release of the drug was observed, indicating that NLC could prolong the release of ATRA. The initial drug concentration affected the photodegradation rate but did not affect the release rate. All ATRA-loaded NLC formulations exhibited the photoprotective property. The cytotoxicity results showed that all ATRA-loaded NLC had higher cytotoxicity than the free drug and HL-60 cells were more sensitive to ATRA than HepG2 cells.

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NLCs are second generation of lipid nanoparticles which have many advantages that make them interesting for topical drugs delivery systems. All-trans retinoic acids (ATRAs) are highly lipophilic and instable in the presence of air, light and heat. In this study, 0.3% ATRAs loaded NLCs were developed by de novo emulsifications, then were reduced to nanometer range by ultrasonicator. The characterizations of NLCs i.e. size and zeta potential were examined. NLCs with different solid:liquid lipids ratios (2:1, 1:1 and 1:2), were formulated in order to maximize the skin permeation. The results demonstrate the sizes of NLCs were in nanometer ranges with negative zeta potential. Moreover the results showed that the amount of solid lipids in the formulation affected the skin permeation. The highest ATRAs permeations though shed snake skin could be achieved from the NLCs which lipid matrixs were composed of 2:1 solid:liquid lipids ratios.