Microfabricated Drug Delivery Systems: Concepts to Improve Clinical Benefit

被引:44
作者
Martin, Frank J. [1 ,2 ]
Grove, Carl [1 ]
机构
[1] iMEDD Inc, Columbus, OH 43212 USA
[2] ALZA Corp, Menlo Pk, CA 94025 USA
关键词
microfabrication; bioMEMS; drug delivery; nanopore membranes; microparticles; peptides; proteins;
D O I
10.1023/A:1011442024658
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Important classes of drugs have yet to benefit from advances in drug delivery technology. Strategies to provide reasonable oral bioavailability of peptide and proteins drugs remain elusive, for example. Systemic cancer drugs produce dose-limiting toxicities largely due to their lack of selectivity. Although delivery systems such as immunotoxins and liposomes improve selectivity of a few cancer drugs, current technology is not suitable for the vast majority of such molecules. Systems able to mimic the body's natural feedback mechanisms for secretion of hormones such as insulin represents yet another unmet medical need. Microfabrication techniques may permit the creation of drug delivery systems that possess a combination of structural, mechanical, and perhaps electronic features which may surmount some of these challenges. In this review, drug delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells-as a possible treatment for diabetes-and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug-loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs. Similarly designed particles with sizes in the 2-10 mu m range may be safe to administer intravenously and a clinical strategy is suggested for using such microparticles for treating solid tumors. Although hypothetical now, work is in progress to prove the concepts presented here and to validate the intuitive belief that there is an important place for microfabricated systems in drug delivery.
引用
收藏
页码:97 / 107
页数:11
相关论文
共 57 条
  • [31] Kim HK, 1999, BIOTECHNOL BIOENG, V65, P659, DOI 10.1002/(SICI)1097-0290(19991220)65:6<659::AID-BIT6>3.0.CO
  • [32] 2-9
  • [33] Korth-Bradley JM, 2000, ANN PHARMACOTHER, V34, P161
  • [34] MAINTENANCE OF NORMOGLYCEMIA IN DIABETIC MICE BY SUBCUTANEOUS XENOGRAFTS OF ENCAPSULATED ISLETS
    LACY, PE
    HEGRE, OD
    GERASIMIDIVAZEOU, A
    GENTILE, FT
    DIONNE, KE
    [J]. SCIENCE, 1991, 254 (5039) : 1782 - 1784
  • [35] Lanza Robert P., 1999, Molecular Medicine Today, V5, P105, DOI 10.1016/S1357-4310(99)01440-9
  • [36] Encapsulated cell technology
    Lanza, RP
    Hayes, JL
    Chick, WL
    [J]. NATURE BIOTECHNOLOGY, 1996, 14 (09) : 1107 - 1111
  • [37] MEASUREMENT OF RAT LUNG BLOOD-FLOW WITH LABELED MICROSPHERES
    LATRES, E
    CLOSA, D
    GOMEZSIERRA, JM
    ALEMANY, M
    REMESAE, X
    [J]. ARCHIVES INTERNATIONALES DE PHYSIOLOGIE DE BIOCHIMIE ET DE BIOPHYSIQUE, 1992, 100 (03): : 263 - 265
  • [38] Lectin-mediated drug delivery: The second generation of bioadhesives
    Lehr, CM
    [J]. JOURNAL OF CONTROLLED RELEASE, 2000, 65 (1-2) : 19 - 29
  • [39] LIOTTA LA, 1993, CANC PRINCIPLES PRAC, P134
  • [40] MORROW CS, 1993, CANC PRINCIPLES PRAC, P340