Abstract
Restricted drug entry to the brain that is closely associated with the existence of the blood brain barrier (BBB) has limited the accessibility of most potential active therapeutic compounds to the brain from the systemic circulation. Recently, evidences for the presence of direct nose-to-brain drug transport pathways have been accumulated by several studies and an intranasal drug administration route has gained attention as a promising way for providing direct access to the brain without the needs to cross to the BBB. Studies aiming for developing nanoparticles as an intranasal drug carrier have shown considerable promise in overcoming the challenges of intranasal drug delivery route. This review gives a comprehensive overview of works having investigated liposomes as a potential vehicle to deliver drugs to the brain through nose-to-brain route while considering the excellent biocompatibility and high potential of liposomes for clinical development. Herein, studies are reviewed with special emphasis on the impact of formulation factors, such as liposome composition and surface modification of liposomes with targeting moieties, in addition to intranasal environmental factors that may affect the extent/site of absorption of intranasally administered, liposome-encapsulated drugs.
Highlights
A number of patients suffering from neurodegenerative diseases and other central nervous system (CNS) disorders has shown a continuous increase that is associated with the aging population during the last decade
The present review summarizes the transport mechanisms by which nasally administered drugs gain access to the brain first, followed by a comprehensive overview of the latest progress in the field of liposome formulation as an intranasally administered carrier
Studies for developing nanoparticle formulations aiming at enhancing the nose-to-brain drug delivery have shown considerable promise for the future
Summary
A number of patients suffering from neurodegenerative diseases and other central nervous system (CNS) disorders has shown a continuous increase that is associated with the aging population during the last decade. Effective therapeutic agents to treat most of these diseases are still missing, mainly due to the complicated, multifactorial pathogenic mechanisms [2] Another major hurdle in the treatment of CNS diseases is the very limited accessibility of most potential active therapeutic compounds to the brain from the systemic circulation, which results in drug levels reaching the target site being insufficient to exert the pharmacological effect [3]. Several potential advantages of intranasal administration have been proposed from these studies They include the easy accessibility of the nasal cavity allowing for self-administration, improved patient compliance, rapid onset of action, minimized systemic exposure and reduced potential peripheral side effects, raising a possibility of clinical development of a dosage form with multiple benefits, in addition to an improved drug bioavailability in the brain [2,18]. Implications and future perspectives will be given to better understand and give insight in developing liposomal formulations for nose-to-brain drug delivery
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