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.
Highlights
Dacarbazine (Dac), a highly lipid-soluble and light-sensitive agent chemically known as 5-(3,3-dimethyl-1-triazenyl) imidazole-4-carboxamide, is an antineoplastic drug that has been used to treat various cancers [1]
nanostructured lipid carriers (NLCs)/PI-Dac developed in this study showed a relative earlier drug release as compared with the formulation reported by Ding et al [15, 16], it has been demonstrated that a drug encapsulated in NLC with a similar in vitro release profile as NLC/PI-Dac developed in this study could reach the brain 2 h after intravenous injection [29]
This study implicates that NLC could have the potential for drug delivery via multiple routes. This is the first report on the development of NLCs for Dac delivery
Summary
Dacarbazine (Dac), a highly lipid-soluble and light-sensitive agent chemically known as 5-(3,3-dimethyl-1-triazenyl) imidazole-4-carboxamide, is an antineoplastic drug that has been used to treat various cancers [1]. It is the only US Food and Drug Administration (FDA)-approved chemotherapeutic agent for treating wild-type melanoma, a skin cancer that accounts for the vast majority of skin cancer deaths [2, 3]. It is the most active single agent currently used for treating metastatic melanoma [4]. No treatment can prolong the overall survival of the disease
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