Biodistribution and Pharmacokinetic Studies of Bone-Targeting N-(2-Hydroxypropyl)methacrylamide Copolymer−Alendronate Conjugates

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• 作者：Huaizhong Pan ; Monika Sima ; Pavla Kopec&#780 ; ková ; Kuangshi Wu ; Songqi Gao ; Jihua Liu ; Dong Wang ; Scott C. Miller ; Jindr&#780 ; ich Kopec&#780 ; ek
• 刊名：Molecular Pharmaceutics
• 出版年：2008
• 出版时间：August 2008
• 年：2008
• 卷：5
• 期：4
• 页码：548-558
• 全文大小：206K
• 年卷期：v.5,no.4(August 2008)
• ISSN：1543-8392

文摘

The biodistribution and pharmacokinetics of bone-targeting N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer−alendronate conjugates were evaluated following intravenous administration of radioiodinated conjugates to young healthy BALB/c mice. The synthesis of a polymerizable and cathepsin K cleavable alendronate derivative, N-methacryloylglycylglycylprolylnorleucylalendronate, enabled the preparation of HPMA copolymer−alendronate conjugates with varying composition. Using the RAFT (reversible addition−fragmentation chain transfer) polymerization technique, four conjugates with different molecular weight and alendronate content and two control HPMA copolymers (without alendronate) with different molecular weight were prepared. The results of biodistribution studies in mice demonstrated a strong binding capacity of alendronate-targeted HPMA copolymer conjugates to bone. Conjugates with low (1.5 mol%) alendronate content exhibited a similar bone deposition capacity as conjugates containing 8.5 mol % of alendronate. The molecular weight was an important factor in the biodistribution of the HPMA copolymer conjugates. More conjugate structures need to be evaluated, but the data suggest that medium molecular weights (50−100 kDa) might be effective drug carriers for bone delivery.