Strategies for enhanced drug delivery to the central nervous system

Abstract

Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system.

Keywords: CNS drug delivery; blood brain barrier; nano particles; p-glycoprotein.

Fig. 1

Schematic comparison between brain and general capillaries. The epithelium in brain capillaries are thickened with fat which acts as tight junctions and barrier for water soluble molecules in systemic circulation.

Fig. 2

The lock-in mechanism for a brain chemical drug delivery system (CDDS). Lipid soluble drug after entering the brain gets converted into less lipid soluble drug by metabolic conversion. The formed metabolite gets entrapped in the brain, which ensures longer residence leading to longer duration of action and targeting action. T- Targeter moiety (lipophilic form); D- drug; F- modifier function; T⁺- Targeter moiety (hudrophilic form).

Fig. 3

Transferrin transporter-based chemical peptide delivery. Peptide like drugs (VIPa) can be delivered to the brain by conjugating them to monoclonal antibodies (TfCRMab) by utilizing transporters such as transferrin transporter. TfT- transferring transporter; TfcRMab- antitransferrin receptor monoclonal antibody; SPDP- N-succinimidyl-3-(2-pyridyldithio)propionate; VIPa- vasoactive intestinal peptide analog.

Fig. 4

The Olfactory pathway between nose and central nervous system. Drugs can be delivered to the CNS by using olfactory route prevailing between nose and brain.

Fig. 5

Structural Similarity between PNA and DNA oligomers. The molecular mimicry of DNA into Polyamide (peptide) nucleic acids (PNAs) has helped the delivery of the chimeric peptide to intra cranial delivery.