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The development of novel drug carriers is invaluable to maximize therapeutic efficiency and improve specificity. Dioctadecyl-dimethylammonium bromide (DODAB): monoolein (MO) (1:2) liposomes exhibit non-lamellar phases in their core that improve the encapsulation ability of both hydrophobic and hydrophilic molecules. This study explores the use of this nanosystem for the therapeutic delivery of cytokines, specifically of leukemia inhibitory factor (LIF). Nanocarriers can overcome the drawbacks of direct cytokine administration, like poor bioavailability.
DODAB:MO (1:2) liposomes were produced by lipid film hydration, followed by extrusion, and used for encapsulating 0.125 and 0.25 µM LIF. The produced nanoparticles were characterized in terms of size and zeta potential, FTIR and STEM. LIF was quantified with an optimized Bradford method to determine encapsulation efficiencies, drug loading, and release profile. Cytotoxicity was assessed by hemolysis, and mouse myoblasts were used to validate bioactivity in vitro.
Neither the extrusion nor the protein incorporation steps promoted significant alterations in cytokine structure. LIF-containing liposomes DODAB (1:2) nanosystem were small (~200-300nm), positively charged (~50-60mV), non-toxic, and stable at physiological pH. Biophysical characterization identified liposomal formulation of 200 µM DODAB:MO (1:2) at 0.25 µM as the most efficient system. The bioactivity analysis showed an increase of ~20% in cell proliferation after 48h of incubation when compared to free mLIF. Also, the LIF-containing DODAB:MO (1:2) liposomal formulation, when exposed to serum, revealed a capacity to protect its cargo for up to 6 h.
The DODAB:MO (1:2) nanosystem was found to be efficient for cytokine delivery, stabilizing mLIF, and promoting its bioactivity with multiple applications.
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