Section Review: Central & Peripheral Nervous Systems: Macromolecular drug delivery to the CNS with protein carriers

Abstract

Site-specific delivery of macromolecules to the CNS constitutes a major problem. If therapeutic macromolecules - peptides, oligonucleotides, labelling agents - could be delivered specifically, it would open up major possibilities for the detection of the onset of degenerative processes, and the monitoring of disease progression and drug action. Delivery systems are needed that meet two criteria: a) the capacity to bring therapeutic quantities of macromolecular agents into the CNS, and b) the ability to direct these agents towards specific populations of neurones. Entering the CNS means crossing the blood-brain or blood-cerebrospinal fluid barriers. Various strategies have been developed to transport macromolecular agents into the CNS across these barriers, such as direct intracranial or intrathecal delivery with minipumps, sustained-release microcapsules, and implants or grafted microcapsules containing genetically modified somatic cells. Initial preclinical results with these technologies have been encouraging, but they are not yet designed to target efficiently specific regions within the CNS or specific neurone populations, nor are they easily applicable. Protein vectors for CNS delivery is an emergent technology that may provide an efficient solution for the selective targeting of macromolecular agents to the CNS. In this review, the present state of this technology is discussed and is compared to current technologies.

Key Words:

• antibody
• binding
• biodegradable microcapsules
• central nervous system
• drug delivery
• encapsulated agent
• genetically modified cell
• infusion
• internalisation
• microencapsulated somatic cell
• minipump
• neurodegeneration
• neurotoxin
• neurotrophic protein carrier
• neurotrophin
• olfactory neurone
• receptor targeting
• retrograde transport
• transporting moiety