Drug delivery to tumors of the central nervous system.
Contemporary treatment of malignant brain tumors has been hampered by problems with drug delivery to the tumor bed. Inherent boundaries of the central nervous system, such as the blood-brain barrier or the blood-cerebrospinal fluid barrier, and a general lack of response to many chemotherapeutic agents have led to alternative treatment modalities. In general, all these modalities have sought to either disrupt or bypass the physiologic brain barriers and deliver the drug directly to the tumor. This article reviews past, as well as current, methods of drug delivery to tumors of the central nervous system. Special emphasis is placed on biodegradable polymers that can release chemotherapeutic agents against malignant gliomas. A variety of other nonchemotherapeutic drugs, including antiangiogenesis and immunotherapeutic agents, are presented in the context of new polymer technology. Finally, future directions in drug delivery are discussed with an overview on new advances in emerging biotechnology.
Lesniak
M S
MS
Departments of Neurological Surgery and Oncology, Johns Hopkins Hospital, Hunterian 817, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Langer
R
R
Brem
H
H
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001673:Biodegradation, Environmental; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004337:Drug Carriers; D004343:Drug Implants; D005544:Forecasting; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D006801:Humans; D015552:Injections, Intralesional; D007278:Injections, Spinal; D015993:Life Tables; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011108:Polymers; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004337:Drug Carriers; D004343:Drug Implants; D009607:Nitrosourea Compounds; D011108:Polymers; D011355:Prodrugs; C453779:carmustine with prolifeprosan 20; D002330:Carmustine