Therapeutic potential of controlled drug delivery systems in neurodegenerative diseases.
Several compounds that exhibit a therapeutic effect in experimental models of neurodegenerative diseases have been identified over recent years. Safe and effective drug delivery to the central nervous system is still one of the main obstacles in translating these experimental strategies into clinical therapies. Different approaches have been developed to enable drug delivery in close proximity to the desired site of action. In this review, we describe biodegradable polymeric systems as drug carriers in models of neurodegenerative diseases. Biomaterials described for intracerebral drug delivery are well tolerated by the host tissue and do not exhibit cytotoxic, immunologic, carcinogenic or teratogenic effects even after chronic exposure. Behavioral improvement and normalization of brain morphology have been observed following treatment using such biomaterials in animal models of Parkinson's, Alzheimer's and Huntington's diseases. Application of these devices for neuroactive drugs is still restricted due to the relatively small volume of tissue exposed to active compound. Further development of polymeric drug delivery systems will require that larger volumes of brain tissue are targeted, with a controlled and sustained drug release that is carefully controlled so it does not cause damage to the surrounding tissue.
Popovic
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N
Neuronal Survival Unit, Department of Experimental Medical Science, BMC A10, 22 184 Lund, Sweden. natalija.popovic@med.lu.se
Brundin
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P
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001921:Brain / Q000378:metabolism; D003692:Delayed-Action Preparations; D004058:Diffusion; D004195:Disease Models, Animal; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy; D007980:Levodopa / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D008863:Microspheres; D020932:Nerve Growth Factor / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D020734:Parkinsonian Disorders / Q000188:drug therapy; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry; D012995:Solubility
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D018696:Neuroprotective Agents; D011108:Polymers; D007980:Levodopa; D020932:Nerve Growth Factor