Fucoidan-coated lipid nanocapsules encapsulating a model drug for lung drug delivery

 

Jorge F. Pontes1, Emanuel Duarte2, Noelia Flórez-Fernandez1,2,3, João Rico2, Joana Cruz2, Giovanna Lollo4, & Ana Grenha1,2

1Centre for Marine Sciences, Drug Delivery Laboratory, Universidade do Algarve, Campus de Gambelas, Faro, 8005-139, Portugal

2Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus Gambelas, Faro, 8005-139, Portugal

3Faculty of Sciences, University of Vigo, Campus As Lagoas, Ourense, Spain

4University of Lyon, Université Claude Bernard Lyon 1, LAGEPP CNRS, UMR 5007, Villeurbanne, France

 

Lipid nanocapsules (LNC), comprised of an oily core and an outer polymeric shell, have been proposed for the delivery of hydrophobic drug molecules. LNC can be formed almost instantaneously by solvent displacement technique, a method involving the mixture of two phases of opposite polarities. This work proposes LNC comprised of an oily core of positively charged lecithin (1,2-dioleoyloxy-3-trimethylammoniumpropanchloride, DOTAP) and medium chain triglycerides (Miglyol® 812), coated with fucoidan (FUC), a sulphated polysaccharide of marine origin, as drug carriers. The selection of the formulation of FUC/DOTAP = 0.5/0.1 (% m/v, total 10 mL) was based on previous studies of stability, excipient concentration, and drug encapsulation capacity. Curcumin (0.75 mg) was associated as model hydrophobic drug. Sizes around 200 nm and strong negative zeta potential (ca. -70 mV) were obtained for unloaded and drug-loaded LNC, no significant changes being observed upon drug association. The LNC revealed stability of the physicochemical parameters when stored at 4 ºC for 30 days. Moreover, a 24 h exposure of alveolar epithelial (A549) cells to curcumin-loaded nanocapsules at curcumin concentrations up to 20 µg/mL did not induce cell toxicity (cell viability > 70%) and demonstrated the capacity of LNC to mitigate the cytotoxicity of the drug. In fact, free curcumin induced cell viability below 70% and resulted in half maximal inhibitory concentration (IC50) of 3.59 µg/mL. Envisaging an application in lung delivery, LNC were microencapsulated by spray-drying, using mannitol as matrix material (Mannitol/LNC = 85/15 (w/w)), a process under optimisation to attain adequate aerodynamic characteristics.

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