Multidrug-loaded liposomes prevent ischemic stroke through intranasal administration

Area of Science:

• Neuroscience
• Pharmacology
• Biotechnology

Background:

• Baicalin (BA) exhibits neuroprotective properties but suffers from poor solubility and low bioavailability.
• Ischemic stroke (IS) poses a significant health challenge, necessitating effective therapeutic strategies.
• Current treatments for IS often face limitations in efficacy and delivery.

Purpose of the Study:

• To develop and evaluate multidrug-loaded liposomes (BBC-LP) for enhanced intranasal delivery of baicalin, borneol, and cholic acid.
• To investigate the neuroprotective efficacy of BBC-LP in a rat model of ischemic stroke.
• To explore the underlying mechanisms of BBC-LP in treating IS using network pharmacology.

Main Methods:

• BBC-LP were prepared using the reverse evaporation method.
• Liposome characteristics including encapsulation efficiency (EE), drug loading (DL), particle size, and zeta potential were determined.
• Pharmacodynamic and toxicity studies were conducted in middle cerebral artery occlusion (MCAO) rat models.

Main Results:

• Optimized BBC-LP exhibited favorable characteristics: EE of 42.69%, DL of 6.17%, mean particle size of 156.62 nm, PDI of 0.195, and zeta potential of -0.99 mV.
• Intranasal administration of BBC-LP significantly improved neurological deficits, reduced brain infarct volume, and mitigated cerebral pathology in MCAO rats compared to BBC alone.
• Toxicity studies confirmed that BBC-LP was non-irritating to the nasal mucosa.

Conclusions:

• BBC-LP offers a safe and effective strategy for intranasal delivery to ameliorate IS injury.
• The neuroprotective effects of BBC-LP may involve the modulation of the PI3K/Akt and MAPK signaling pathways, leading to anti-apoptotic and anti-inflammatory actions.
• This liposomal formulation holds promise for the treatment of ischemic stroke.