Challenges in design and characterization of ligand-targeted drug delivery systems.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleChallenges in design and characterization of ligand-targeted drug delivery systems.
Publication TypeJournal Article
Year of Publication2012
AuthorsMuro, S
JournalJ Control Release
Date Published2012 Dec 10
KeywordsAnimals, Drug Delivery Systems, Drug Design, Humans, Ligands

Targeting of therapeutic agents to molecular markers expressed on the surface of cells requiring clinical intervention holds promise to improve specificity of delivery, enhancing therapeutic effects while decreasing potential damage to healthy tissues. Drug targeting to cellular receptors involved in endocytic transport facilitates intracellular delivery, a requirement for a number of therapeutic goals. However, after several decades of experimental design, there is still considerable controversy on the practical outcome of drug targeting strategies. The plethora of factors contributing to the relative efficacy of targeting makes the success of these approaches hardly predictable. Lack of fully specific targets, along with selection of targets with spatial and temporal expression well aligned to interventional requirements, pose difficulties to this process. Selection of adequate sub-molecular target epitopes determines accessibility for anchoring of drug conjugates and bulkier drug carriers, as well as proper signaling for uptake within the cell. Targeting design must adapt to physiological variables of blood flow, disease status, and tissue architecture by accommodating physicochemical parameters such as carrier composition, functionalization, geometry, and avidity. In many cases, opposite features need to meet a balance, e.g., sustained circulation versus efficient targeting, penetration through tissues versus uptake within cells, internalization within endocytic compartment to avoid efflux pumps versus accessibility to molecular targets within the cytosol, etc. Detailed characterization of these complex physiological factors and design parameters, along with a deep understanding of the mechanisms governing the interaction of targeted drugs and carriers with the biological environment, are necessary steps toward achieving efficient drug targeting systems.

Alternate JournalJ Control Release
PubMed ID22709588
PubMed Central IDPMC3481020
Grant ListR01 HL098416 / HL / NHLBI NIH HHS / United States
R01-HL98416 / HL / NHLBI NIH HHS / United States