期刊
ANNALS OF PHARMACOTHERAPY
卷 34, 期 7-8, 页码 915-923出版社
SAGE PUBLICATIONS INC
DOI: 10.1345/aph.10054
关键词
polyethylene glycol; liposomes; polymers; polylactic acid; controlled release
OBJECTIVE: To review recent developments in novel injectable drug delivery mechanisms and outline the advantages and disadvantages of each. DATA SOURCES: A MEDLINE (1995-January 2000) search using the terms polyethylene glycol, liposomes, polymers, polylactic acid,and controlled release was conducted. Additional references were identified by scanning bibliographies. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for inclusion. Abstracts were included only if they were judged to add critical information not otherwise available in the medical literature. DATA SYNTHESIS: A number of systems that alter the delivery of injectable drugs have been developed in attempts to improve pharmacodynamic and pharmacokinetic properties of therapeutic agents. New drug delivery systems can be produced either through a change in formulation (e.g., continuous-release products, liposomes) or an addition to the drug molecule (e.g., pegylation). Potential advantages of new deliver mechanism include an increased or prolonged duration of pharmacologic activity, a decrease in adverse effects, and increased patient compliance and quality of life. Injectable continuous-release systems delivery drugs in a controlled, predetermined fashion and are particularly appropriate when it si important to avoid large fluctuations in plasma drug concentrations. Encapsulating a drug within a liposome can produce a prolonged half-life and a shift of distribution toward tissues wit increased capillary permeability (e.g., tumors, infected tissue). Pegylation provides a method for modification of therapeutic proteins to minimize many of the limitations (e.g., poor stability, short half-life, immunogenicity) associated with these agents. CONCLUSIONS: Pegylation of therapeutic proteins is an established process wit new applications. However, not all pegylated proteins are alike, and each requires optimization on a protein-by-protein basis to derive maximum clinical benefit. The language required to describe ech pegylated therapeutic protein must be more precise to accurately distinguish each protein's differential pharmacologic properties.
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