Modulating antibody pharmacokinetics using hydrophilic polymers.
Expert Opin Drug Deliv
; 8(9): 1221-36, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21854300
ABSTRACT
INTRODUCTION:
The use of hydrophilic polymers as a substitute for the Fc-domain in immuno- or non-immuno-based binding proteins is accelerating. Chemical PEGylation has led the way and is still the most advanced and clinically-approved approach. Hydrophilic polymers act by maintaining a flexible conformation and hydrogen bonding to a network of water molecules to acquire a larger hydrodynamic volume and apparent mass than their actual molecular mass suggest. The benefits are increased blood half-life and bioavailability, stability and reduced immunogenicity. In the case of PEG, there is also evidence of enhanced targeting and reduced side effects, but drawbacks include the fact that PEG is non-biodegradable. AREAS COVERED This report reviews the state of the art for antibody PEGylation in terms of approaches and effects. Additionally, non-biological (such as N-(2-hydroxypropyl)methacrylamide) and potentially superior biological alternatives (such as polysialylation) are described, ending with recombinant approaches (such as hydrophilic peptides and glyco-engineering), which promise to circumvent the need for chemical modification altogether. EXPERT OPINION The emergence of many small, antibody fragment-like mimics will drive the need for such technologies, and PEGylation is still the choice polymer due to its established use and track record. However, there will be a place for many alternative technologies if they can match the pharmacokinetics of PEG-conjugates and bring addition beneficial features such as easier production.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Anticuerpos Monoclonales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Deliv
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido