Development of nanostructured lipid carrier for dacarbazine delivery

Abstract

Dacarbazine (Dac) is one of the most commonly used chemotherapy drugs for treating various cancers. However, its poor water solubility, short half-life in blood circulation, low response rate and high side effect limit its application. This study aimed to improve the drug solubility and prolong drug release by developing nanostructured lipid carriers (NLCs) for Dac delivery. The NLC and Dac-encapsulated NLC were synthesized with precirol ATO 5 and isopropyl myristate as lipids, tocopheryl polyethylene glycol succinate, soybean lecithin and Kolliphor P 188 as co-surfactants. The NLCs with controlled size were achieved using high shear dispersion following solidification of oil-in-water emulsion. For Dac encapsulation, the smallest NLC with 155 ± 10 nm in size, 0.2 ± 0.01 polydispersion index and -43.4 ± 2 mV zeta potential was selected. The resultant DLC-Dac possessed size, polydispersion index and zeta potential of 190 ± 10, 0.2 ± 0.01, and -43.5 ± 1.2, respectively. The drug encapsulation efficiency and drug loading were 98.5 % and 14 %, respectively. In vitro drug release study showed a biphasic pattern, with 50 % released in the first 2 h, and the remaining released sustainably for up to 30 h. This is the first report on the development of NLC for Dac delivery, implying that NLC could be a new potential candidate as drug carrier to improve the therapeutic profile of Dac.

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

“…However, its highly lipophilic nature and short half-life hinder its application. The incorporation of dacarbazine in NLCs resulted in a biphasic drug release whereby 50% of the drug got released within the first 2 h while the rest was slowly released for up to 30 h [85]. Accordingly, with proper dose adjustment, this approach can be used in optimizing the clinical effect of dacarbazine and similar drugs with a half-life of less than one hour after intravenous administration [86].…”

Enhanced delivery of melatonin loaded nanostructured lipid carriers duringin vitrofertilization: NLC formulation, optimization and IVF efficacy

“…47 It was then followed by drug release from lipid matrix, 48 which was associated with slow and controlled release for 48 h. However, the release rate of drug soared from suspension, so that 92% of drug was released in the rst 2 h. Similarly, this drug release prole was observed for hydrophobic Dacarbazine drug in the NLC structure. 49…”

Polymeric curcumin nanoparticles by a facile in situ method for macrophage targeted delivery

“…ISCurNP revealed rapid aggregation in the absence of a stabilizer necessitating addition of stabilizer(s) to ensure a uniform and stable nanodispersion. Kolliphor P188 (polyoxyethylene‐polyoxypropylene block‐co‐polymer) is reported as a stabilizer for nanosystems . Soluplus® (polyvinyl caprolactam‐polyvinyl acetate‐polyethyleneglycol graft copolymer) is reported to effectively stabilize wet milled fenofibrate NPs by decreasing the interfacial tension .…”

“…Kolliphor P188 (polyoxyethylene-polyoxypropylene block-co-polymer) is reported as a stabilizer for nanosystems. [23][24][25] Soluplus ® (polyvinyl caprolactam-polyvinyl acetate-polyethyleneglycol graft copolymer) is reported to effectively stabilize wet milled fenofibrate NPs by decreasing the interfacial tension. 26 Figure S1).…”