Challenges in the Design of Clinically Useful Brain-Targeted Drug Nanocarriers

ISSN: 1875-533X (Online)
ISSN: 0929-8673 (Print)


Volume 21, 38 Issues, 2014


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Current Medicinal Chemistry

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Challenges in the Design of Clinically Useful Brain-Targeted Drug Nanocarriers

Author(s): Luca Costantino, Diana Boraschi and Mike Eaton

Affiliation: University of Modena e Reggio Emilia, Dipartimento di Scienze della Vita, Via Campi 183, 41100 Modena, Italy

Abstract

Nowadays, the delivery of drugs by means of intravenously administered nanosized drug carriers - polymer-drug conjugates, liposomes and micelles, is technically possible. These delivery systems are mainly designed for tumour therapy, and accumulate passively into tumours by means of the well known EPR effect. Targeted nanocarriers, that additionally contain ligands for receptors expressed on cell surfaces, are also widely studied but products of this kind are not marketed, and only a few are in clinical trial. Polymeric nanoparticles (Np) able to deliver drugs to the CNS were pioneered in 1995; a number of papers have been published dealing with brain-targeted drug delivery using polymeric Np able to cross the BBB, mainly for the treatment of brain tumours. At present, however, the translation potential of these Np seems to have been exceeded by targeted liposomes, a platform based on a proven technology. This drug delivery system entered clinical trials soon after its discovery, while the challenges in formulation, characterization and manufacturing of brain-targeted polymeric Np and the cost/benefit ratio could be the factors that have prevented their development. A key issue is that it is virtually impossible to define the in vivo fate of polymers, especially in the brain, which is a regulatory requirement; perhaps this is why no progress has been made. The most advanced Np for brain tumours treatment will be compared here with the published data available for those in clinical trial for tumours outside the CNS, to highlight the knowledge gaps that still penalise these delivery systems. At present, new approaches for brain tumours are emerging, such as lipid Np or the use of monoclonal antibody (mAb)-drug conjugates, which avoid polymers. The success or failure in the approval of the polymeric Np currently in clinical trials will certainly affect the field. At present, the chances of their approval appear to be very low

Keywords: Blood-brain barrier, carriers, CNS, drug delivery, glioma, liposomes, nanoparticles, targeting, tumours

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Article Details

Volume: 21
First Page: 1
Last Page: 20
Page Count: 20
DOI: 10.2174/0929867321666140716101921
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