Nanostructured Lipid Carriers (NLC) for Parenteral Delivery of an Anticancer Drug

Abstract

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.

Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity ofall-transretinoic acid

“…Lipid nanocarriers such as nanoemulsions, solid lipid nanoparticles (SLN), and, more recently, nanostructured lipid carriers (NLC) have been studied as alternatives to enable intravenous administration of ATRA [8,9,10]. …”

“…The presence of liquid lipid increases the number of imperfections in the solid lipid matrix, allowing greater accommodation for the drug and decreasing its expulsion over time [12]. In recent years, some studies have been developed using NLC loaded with ATRA for the treatment of cancer [10,13]. …”

Nanostructured lipid carriers as a delivery system of biochanin A

“…In recent years, much works have been focused on the preparation of SLN of poor water-soluble drugs for improving bioavailability (Chirio et al, 2011;Bhandari & Kaur, 2013;Huang et al, 2013). Nonetheless, there were also some limitations of the SLN system, such as limited drug loading capacity due to the solubility of the drug in the solid lipid and drug expulsion during storage (when lipid crystallizes to the stable b-form) (Chinsriwongkul et al, 2011). To overcome these limitations of SLN described above, nanostructured lipid carriers (NLC) were introduced as the SLN of a new generation by blending solid lipid with certain content of liquid lipid.…”

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review

“…140 NLCs based on oleic acid enhanced the ATRA loading capacity in the NLCs; however, all ATRA-loaded NLCs had prolonged release of ATRA in addition to being more cytotoxic than the free drug in an in vitro model of leukemia and hepatic cancer cells. 140 ATRA-loaded NLCs could also be assessed in OSCC because retinoic acid is also effective at preventing the development of oral cancers.…”

“…140 NLCs based on oleic acid enhanced the ATRA loading capacity in the NLCs; however, all ATRA-loaded NLCs had prolonged release of ATRA in addition to being more cytotoxic than the free drug in an in vitro model of leukemia and hepatic cancer cells. 140 ATRA-loaded NLCs could also be assessed in OSCC because retinoic acid is also effective at preventing the development of oral cancers. 141,142 Liu et al designed DTX-loaded NLCs (DTX-NLCs) based on stearic acid, glyceryl monostearate, soya lecithin, and oleic acid prepared by the modified film ultrasonicationdispersion method.…”