Development of Liposome-Based Drug Delivery Systems for Stroke Treatment

The nature of liposomes is phospholipid and cholesterol, which makes them biologically inert, non-immunogenic, and biodegradable, with low intrinsic toxicity. Therefore, they become more potential drug delivery carriers. Despite their lipophilic properties, liposomes are very large and cannot simply diffuse to the cell membrane or between blood brain barrier (BBB) cells. Instead, liposomes cross the BBB via transport systems such as adsorptive-mediated transcytosis (AMT), receptor-mediated transcytosis (RMT), and carrier-mediated transports (CMT). In a sense, liposomes themselves add physiological interactions to the physiological interactions of drugs, thus affecting drug distribution characteristics. Liposomes were designed and optimized to make them more suitable for drug delivery. Ace Therapeutics provides comprehensive services from different perspectives to optimize liposome - based drug delivery systems for stroke treatment.

Preparation of Liposomal Formulations

The first step in establishing a liposome drug delivery system is to prepare liposomes. Ace Therapeutics provides comprehensive services to prepare liposomal formulations. Common preparation methods include the passive drug loading method and the active drug loading method.

• Passive drug loading methods include film divergence, reverse evaporation, secondary emulsification, solvent injection, freeze-drying / melting, and detergent removal.
• Active drug loading methods include the pH gradient method, ammonium sulfate gradient method, calcium acetate gradient method, and ionophore method.

Development of Liposome Systems for BBB Transport

Through surface functionalization and other technologies, some liposomal transport systems utilizing BBB have been developed to efficiently deliver drugs to the brain. Ace Therapeutics provides comprehensive services to develop appropriate liposomal transport systems for stroke pathology.

• Cationic Liposomes
  Surface positively charged liposomes can mediate electrostatic interactions with negatively charged sugar sacs on the luminal BBB membrane to initiate AMT.
• Long-Circulating Liposomes
  Prolonged cycle surface modifications that lead to higher brain absorption include polyethylene glycol covalently bound to liposomal surfaces. This protects liposomes from binding to protein plasma, preventing opsonization activity and subsequent liposomal clearance.
• Targeted Liposomes Using Various Ligands
  Common ligands include the transferrin receptor, GLUT-1 transporter, GSH transporters, nicotinic acetylcholine receptor, and some targeted peptides with shorter amino acids.

Preclinical Evaluation of Liposome Systems for Stroke Treatment

After obtaining liposome preparations, it is very important to evaluate them in vitro and in vivo. Studies have shown that empty liposomes can affect drug BBB transport in a drug-dependent manner. Therefore, the activity evaluation of liposome preparations determines the value of candidate preparations. Therefore, Ace Therapeutics offers a range of services to test the activity of liposome preparations.

• We have developed different in vitro models to examine the toxic effects of liposomal preparations on normal and poststroke nerve cells, internalization mechanisms, transfection efficiency in vitro, and transport in the BBB model.
• We have developed different in vivo models to examine the biodistribution and biocompatibility of liposome preparations in physiological states.
• Given that neurotransmitters have been shown to help lipid nanosomal particles cross the BBB, we examine the interaction between neurotransmitters and liposomes.

Measurement of BBB Permeability

Ace Therapeutics offers comprehensive services to measure the ability of liposomal drugs to cross the BBB while performing pharmacokinetic testing of liposomal drugs.

• We have developed in vitro and in vivo models of the BBB to evaluate the ability of liposomal drugs to penetrate the BBB.
• We perform pharmacokinetic analyses of liposomal drugs, including internal and external clearance rates, brain / blood partitioning coefficients, drug brain tissue distribution volume, and intracerebral half-life.

If you would like to learn more about our services, please feel free to contact us.

1. Bruch, G. E., et al., Liposomes for drug delivery in stroke. Brain Res Bull, 2019. 152: p. 246-256.