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 80
- Downloads 0
The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1
CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of...
Choice of LC-MS Methods for the Absolute Quantification of Drug-Metabolizing Enzymes and Transporters in Human Tissue: a Comparative Cost Analysis
The online version of this article (doi:10.1208/s12248-014-9712-6) contains supplementary material, which is available to authorized users.
Nanoparticles Containing Anti-inflammatory Agents as Chemotherapy Adjuvants: Optimization and In Vitro Characterization
The pre-administration of dexamethasone (DEX) has previously been shown to enhance the anti-tumor efficacy of chemotherapeutic agents. The delivery of anti-inflammatory agents specifically to tumors via nanoparticle carr...
Rapid in vivo oral screening in rats: Reliability, acceptance criteria, and filtering efficiency
The reliability and acceptance criteria of rapid oral exposure screening were evaluated by pharmacokinetic simulations and by comparing oral exposure of 100 proprietary compounds from 15 therapeutic programs obtained at...
Bioequivalence for Locally Acting Nasal Spray and Nasal Aerosol Products: Standard Development and Generic Approval
Demonstrating bioequivalence (BE) for nasal spray/aerosol products for local action has been very challenging because the relationship between the drug in systemic circulation and the drug reaching the nasal site of acti...