Development of osmotically active liposomes for nose-to-brain drug delivery

Abstract

The brain as a drug target site remains a pharmaceutical challenge in spite of numerous efforts to enhance drug delivery to the brain. Nasal drug administration has gained interest among researchers, especially in the last decade, as it provides direct drug access into the brain. However, the nasal mucus and the surrounding environment often limit the use of nose as the administration site. Drug carriers such as liposomes have proven to be suitable to entrap a wide range of drugs protecting them from early clearance and degradation by nasal mucus, thus increasing the drug’s potency even in small volumes applicable to the nose. However, the physiological condition of the nose such as its tonicity is an important parameter to consider when developing liposomal drug formulations intended for nasal administration. In this PhD project, liposomes composed of soy-phosphatidylcholine comprised of six anti-inflammatory drugs, entrapped individually, were proven to be osmotically active within nasal tonicity environment. Liposomes shrank or swelled when exposed to a hypertonic or hypotonic environment, respectively. With precise tailoring of liposomal composition, the liposomes sensitivity to osmotic stress could be utilized to achieve controlled drug delivery within the nasal environment. The obtained data provide important information on the osmotic activity of liposomes and build the fundament for further development of innovative nose-to-brain drug delivery systems.