INVESTIGATING LIPOSOME’S IMMUNOGENICITY AND TOXICITY TOWARD MICROGLIA AND NEUROBLASTOMA

Liposomes are promising nanocarriers for treating neurological disorders because they can cross the blood brain barrier, a major obstacle to brain drug delivery [1]. However, depending on their physicochemical properties (size, surface charge, and membrane fluidity), liposomes may induce toxicity and inflammation [2]. Despite extensive research, their interactions with brain cells remain poorly understood. This study investigates how liposome properties influence toxicity and immunogenicity in neural cell models.
Liposomes containing different phospholipids and cholesterol were prepared by thin-film hydration followed by extrusion. Their size and surface charge were characterised using dynamic light scattering and zeta potential analysis, while membrane fluidity values were obtained from the literature. Neuroblastoma (SHSY5Y) and microglial (HMC3) cell lines were treated with liposomes at concentrations ranging from 0.001 to 1 mg/mL for 6, 24, and 48 h. Cell viability was assessed via Alamar Blue assay (n=3), and immune responses were evaluated by measuring IL-6 and IL-8 secretion using ELISA (n=3) while lipopolysaccharide (LPS) served as a pro-inflammatory control.
Cationic liposomes with surface charges above +40 mV exhibited toxicity in both cell lines at concentrations exceeding 10 µg/mL, resulting in up to 95% cell death. None of the formulations increased IL-6 or IL-8 levels relative to untreated controls, but interestingly, some liposomes attenuated the LPS-induced inflammatory response. Liposome size and membrane fluidity did not affect toxicity or immunogenicity, whereas composition, particularly surface charge, was a key determinant of cytotoxicity in brain cells.
References:
[1] Vieira, D.B. and L.F., 2016, 10.2147/IJN.S117210
[2] Inglut, C.T., et al., 2020, 10.3390/nano10020190