Poly(ethylene glycol)-Modified Proteins: Implications for Poly(lactide-co-glycolide)-Based Microsphere Delivery
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 1
Abstract
The reduced injection frequency and more nearly constant serum concentrations afforded by sustained release devices have been exploited for the chronic delivery of several therapeutic peptides via poly(lactide-co-glycolide) (PLG) microspheres. The clinical success of these formulations has motivated the exploration of similar depot systems for chronic protein delivery; however, this application has not been fully realized in practice. Problems with the delivery of unmodified proteins in PLG depot systems include high initial “burst” release and irreversible adsorption of protein to the biodegradable polymer. Further, protein activity may be lost due to the damaging effects of protein-interface and protein-surface interactions that occur during both microsphere formation and release. Several techniques are discussed in this review that may improve the performance of PLG depot delivery systems for proteins. One promising approach is the covalent attachment of poly(ethylene glycol) (PEG) to the protein prior to encapsulation in the PLG microspheres. The combination of the extended circulation time of PEGylated proteins and the shielding and potential stabilizing effects of the attached PEG may lead to improved release kinetics from PLG microsphere system and more complete release of the active conjugate.
Authors and Affiliations
Sheetal S. Pai, Robert D. Tilton, Todd M. Przybycien
Keywords
Related Articles
- EP ID EP681442
- DOI 10.1208/s12248-009-9081-8
- Views 61
- Downloads 0
Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations, Part 6: Effects of Varying Pancreatin and Calcium Levels
The online version of this article (doi:10.1208/s12248-014-9672-x) contains supplementary material, which is available to authorized users.
Effect of N-1 and N-2 residues on peptide deamidation rate in solution and solid state
The deamidation kinetics of 7 model peptides (VYPNGA, VYGNGA, VFGNGA, VIGNGA, VGGNGA, VGPNGA, and VGYNGA) were studied at 70°C in pH 10 buffer solutions and at 70°C and 50% relative humidity in lyophilize...
Linking human and veterinary health: Trends, directions and initiatives
The objective of this brief article is to provide an overview of some of the important harmonization efforts that are currently under way within the animal health community. Topics include: scientific networks and interd...
Population Pharmacokinetics and Exposure-Uric Acid Analyses After Single and Multiple Doses of ABT-639, a Calcium Channel Blocker, in Healthy Volunteers
ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain. In the current first-in-human (FIH) study, the pharmacokinetics, tolerability...
Aerosolization of lipoplexes using AERx® pulmonary delivery system
The lung represents an attractive target for delivering gene therapy to achieve local and potentially systemic delivery of gene products. The objective of this study was to evaluate the feasibility of the AERx Pulmonary...