Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Pharm Res. 2003 Oct;20(10):1533-8.

pH-triggered release of macromolecules from spray-dried polymethacrylate microparticles.

Author information

  • 1Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

PURPOSE:

pH-triggered microparticles release their therapeutic payloads at acidic pH (e.g., in the phagosome), making intracellular drug delivery more efficient. Here we modify lipid-based microparticles that are safe and efficacious in nerve and brain and are potentially inhalable, making them pH-triggerable by incorporating an acid-soluble polymethacrylate, Eudragit E100 (E100).

METHODS:

Microparticles were produced by spray-drying and characterized by electron microscopy, Coulter counting, density measurement, and release kinetics of fluorescently labeled proteins. In addition, biocompatibility and cellular uptake were observed in rats.

RESULTS:

Microparticles were spheroids 3 to 5 microm in diameter with densities of 0.12 to 0.25 g/L. Microparticles with 20% (w/w) or more E100 demonstrated slow release of fluorescently labeled proteins at pH 7.4 but rapid release at pH 5. pH-triggerability was maintained for over 2 weeks in solution. Protein loadings of 0.2-20% (w/w) were pH-triggerable. Histologic examination of particles in rat connective tissue near nerve and muscle demonstrated biocompatibility aside from muscle edema in the cell layers adjacent to the particles and a localized inflammatory reaction with macrophages laden with microparticles.

CONCLUSIONS:

Microparticles containing E100 were pH-triggerable for many days and were taken up by macrophages, suggesting that they may be useful for intracellular drug delivery.

PMID:
14620503
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk