Perillyl Alcohol and Its Drug-Conjugated Derivatives as Potential Novel Methods of Treating Brain Metastases.
Metastasis to the central nervous system remains difficult to treat, and such patients are faced with a dismal prognosis. The blood-brain barrier (BBB), despite being partially compromised within malignant lesions in the brain, still retains much of its barrier function and prevents most chemotherapeutic agents from effectively reaching the tumor cells. Here, we review some of the recent developments aimed at overcoming this obstacle in order to more effectively deliver chemotherapeutic agents to the intracranial tumor site. These advances include intranasal delivery to achieve direct nose-to-brain transport of anticancer agents and covalent modification of existing drugs to support enhanced penetration of the BBB. In both of these areas, use of the natural product perillyl alcohol, a monoterpene with anticancer properties, contributed to promising new results, which will be discussed here.
Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. thomas.chen@medmail.usc.edu.
Thomas C
TC
Chen
Department of General and Specialized Surgery, Antonio Pedro University Hospital, Fluminense Federal University, Niterói, RJ 24220, Brazil. clovis.orlando@uol.com.br.
Clovis O
CO
Da Fonseca
Department of Molecular Microbiology & Immunology; Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. schontha@usc.edu.
Axel H
AH
Schönthal
D000281:Administration, Intranasal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D039821:Monoterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004337:Drug Carriers; D039821:Monoterpenes; C032208:perillyl alcohol
blood-brain barrier; brain drug delivery; intranasal; metastasis; perillyl alcohol