TY - JOUR
T1 - Synthesis and characterization of branched poly(L-glutamic acid) as a biodegradable drug carrier
AU - Tansey, W.
AU - Ke, S.
AU - Cao, X. Y.
AU - Pasuelo, Marites J.
AU - Wallace, Sidney
AU - Li, Chun
N1 - Funding Information:
Supported in part by grants from the National Cancer Institute (R41-CA80589), the Department of Defense (BC960384), the Texas Higher Education Board (#003657-0042-2001), and the John S. Dunn Foundation. We thank Stephanie Deming for editing the manuscript.
PY - 2004/1/8
Y1 - 2004/1/8
N2 - Polymeric drug delivery systems are used not only to improve aqueous solubility of drug molecules but also to achieve desirable pharmacokinetics and an enhanced therapeutic index. New biodegradable polymers are needed to improve the biodistribution and targeting-ability of polymeric carriers. In this study, the synthesis and characterization of branched poly(L-glutamic acid) (PG) containing multiple PG chains centered on a poly(amidoamine) (PAMAM) dendrimer or polyethyleneimine (PEI) cores were described. The branched PG polymers were obtained by ring-opening polymerization of benzyl ester of L-glutamic acid N-carboxyanhydride using PAMAM or PEI as the initiator. These polymers were degradable in the presence of the lysosomal enzyme cathepsin B, albeit more slowly than linear PG. Unlike conventional linear PG, each branched PG possessed multiple terminal amino groups. This made it possible to attach multiple targeting moieties selectively to the termini of branched PG. Conjugation of monofunctional or heterodifunctional polyethylene glycol to the chain ends of branched PG was demonstrated in the presence of side chain carboxyl groups. Furthermore, folic acid, a model targeting moiety, and the near-infrared dye indocyanine green, a model diagnostic agent, were successfully conjugated to the terminal amino groups and the side chain carboxyl groups of branched PG, respectively. The resulting conjugate had reduced nonspecific interaction and bound selectively to tumor cells expressing folate receptors. Thus, branched PG may be useful as a polymeric carrier for targeted drug delivery.
AB - Polymeric drug delivery systems are used not only to improve aqueous solubility of drug molecules but also to achieve desirable pharmacokinetics and an enhanced therapeutic index. New biodegradable polymers are needed to improve the biodistribution and targeting-ability of polymeric carriers. In this study, the synthesis and characterization of branched poly(L-glutamic acid) (PG) containing multiple PG chains centered on a poly(amidoamine) (PAMAM) dendrimer or polyethyleneimine (PEI) cores were described. The branched PG polymers were obtained by ring-opening polymerization of benzyl ester of L-glutamic acid N-carboxyanhydride using PAMAM or PEI as the initiator. These polymers were degradable in the presence of the lysosomal enzyme cathepsin B, albeit more slowly than linear PG. Unlike conventional linear PG, each branched PG possessed multiple terminal amino groups. This made it possible to attach multiple targeting moieties selectively to the termini of branched PG. Conjugation of monofunctional or heterodifunctional polyethylene glycol to the chain ends of branched PG was demonstrated in the presence of side chain carboxyl groups. Furthermore, folic acid, a model targeting moiety, and the near-infrared dye indocyanine green, a model diagnostic agent, were successfully conjugated to the terminal amino groups and the side chain carboxyl groups of branched PG, respectively. The resulting conjugate had reduced nonspecific interaction and bound selectively to tumor cells expressing folate receptors. Thus, branched PG may be useful as a polymeric carrier for targeted drug delivery.
KW - Biodegradable
KW - Dendrimer
KW - Drug targeting
KW - Multivalency
KW - Poly(L-glutamic acid)
UR - http://www.scopus.com/inward/record.url?scp=0346735304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346735304&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2003.09.005
DO - 10.1016/j.jconrel.2003.09.005
M3 - Article
C2 - 14684270
AN - SCOPUS:0346735304
SN - 0168-3659
VL - 94
SP - 39
EP - 51
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -