Nanomedicine: Delivery of Peptides and Proteins to the Brain Using Nano-Drug Delivery Systems and Other Formulations

Peptides and proteins can potently modulate processes in the central nervous system (CNS) and can be used for management of CNS disorders and other diseases. However, peptides and proteins permeate to a limited extent into the CNS, due to the blood-brain and blood-cerebrospinal fluid barriers, and undergo rapid clearance by endogenous proteases and via other pathways. These pharmacokinetic drawbacks prevent accumulation of peptide and protein drugs in the CNS and render them pharmacologically inefficient. Different approaches for enhanced delivery of peptide/protein drugs to the brain have been developed in order to overcome these drawbacks and to increase their therapeutic efficiency. These approaches include: (a) focal administration into the brain tissue or fluids (via intracerebral, intrathecal, or intracerebroventricular injection), (b) incorporation of drugs into specialized nano-drug delivery systems (DDSs) and other formulations, (c) disruption of CNS barriers, (d) use of immune cells as ‘Trojan horses’ for peptide/protein brain deliver, and others. In this chapter, the major approaches used to deliver peptide and protein drugs to the brain are described and factors that affect the systemic and local drug disposition (distribution and elimination) are summarized. Current problems and limitations in the field of brain delivery of the peptide and protein drugs are presented, and recommendations for further brain delivery enhancement of peptide/protein drugs are given.