Formulation, characterization, and in vitro evaluation of lactoferrin conjugated liposome loaded with magnesium sulfate for improved CNS penetrability.

Abstract

Magnesium deficiency has been reported in association with various disease conditions, particularly in neurological diseases. The limited clinical use of magnesium sulfate is due to its restricted entry into the Central Nervous system (CNS) through blood brain barrier (BBB) which may consequently result in the peripheral accumulation followed by its toxic effects. The current study is focused on the development of nano formulation of lactoferrin conjugated liposome loaded with magnesium sulfate (LMGPLS) with an aim to improve its CNS permeability. LMGPLS was prepared by thin-film hydration technique followed by the lactoferrin conjugation. The average particle size of the LMGPLS was found to be 273.23 ± 6.7 nm. In vitro drug release studies showed that the drug release started after 15 min and continued up to 5 h from LMGPLS. The parallel artificial membrane permeability assay proved the improved lipid layer permeation of prepared formulation when compared with that of the drug solution. The prepared LMGPLS were found to be haemo-compatible and cyto-compatible when tested with blood as well as with multiple cell lines. The pharmacological effects of the formulations were evaluated by multiple in vitro experiments. The results from in vitro experiments showed that the developed formulation is capable of improving the cell viability in glutamate and H₂O₂ treated cell lines indicating its antioxidant and anti-excitotoxicity effects. Additionally, the developed liposome showed significant effect on digoxin induced Na⁺/K⁺ ATPase inhibition. Good lipid layer penetrability with haemo-compatibility and cytocompatibility warrant that the formulation will be a suitable candidate to increase the CNS delivery of Magnesium.