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The Interaction of Cationic Polymers and Their Bisphosphonate Derivatives with Hydroxyapatite
Author(s) -
Zhang Sufeng,
Wright Jennifer E. I.,
Özber Natali,
Uludağ Hasan
Publication year - 2007
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200600286
Subject(s) - cationic polymerization , chemistry , polymer , combinatorial chemistry , in vivo , conjugated system , linker , polyethylene glycol , polymer chemistry , biophysics , organic chemistry , microbiology and biotechnology , computer science , biology , operating system
Conjugating proteins with bisphosphonates (BPs), a class of molecules with exceptional affinity to hydroxyapatite (HA), is a feasible means to impart bone affinity to protein‐based therapeutic agents. To increase the targeting effectiveness while minimizing protein modification, a polymeric linker containing multiple copies of BPs could be constructed for protein conjugation and targeting to bone. Towards this goal, poly( L ‐lysine) (PLL) and poly(ethylenimine) (PEI) were utilized as the polymeric backbones to incorporate a BP, namely 2‐(3‐mercaptopropylsulfanyl)‐ethyl‐1,1‐bisphosphonic acid (thiolBP), by using N ‐hydroxysuccinimidyl polyethylene glycol maleimide and succinimidyl‐4‐( N ‐maleimidomethyl)‐cyclohexane‐1‐carboxylate, respectively. In vitro and in vivo mineral affinity of the polymer‐BP conjugates were determined in comparison with the unmodified polymers. The in vitro results indicated strong binding of the cationic polymers to HA in their unmodified form. BP conjugation did not enhance the inherent mineral affinity of the polymers; in contrast, certain modifications negatively affected the polymers' binding to the HA. In vivo results from a subcutaneous implant model in rats also showed no significant difference in mineral affinity of the BP modified and unmodified PEI. We conclude that thiolBP conjugation to the cationic polymers PLL and PEI was not beneficial for increasing the mineral affinity of the polymeric molecules. The strong interaction between the cationic polymers and HA may make the polymers suitable for imparting mineral affinity to bone‐acting therapeutics.