New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation

被引:60
作者
Giavaresi, G
Tschon, M
Borsari, V
Daly, JH
Liggat, JJ
Fini, M
Bonazzi, V
Nicolini, A
Carpi, A
Morra, M
Cassinelli, C
Giardino, R
机构
[1] Ist Ortoped Rizzoli, Dept Expt Surg, I-40136 Bologna, Italy
[2] Univ Strathclyde, Dept Pure & Appl Chem, Glasgow, Lanark, Scotland
[3] Italia ONLUS Fdn, ANT, Dept Sci Res & Dev, Bologna, Italy
[4] Univ Pisa, Sch Internal Med, Pisa, Italy
[5] Nobil Bio Ric Srl, Villafranca Dasti, Italy
基金
英国工程与自然科学研究理事会;
关键词
drug delivery systems; polymers; polyesters; polyphosphazenes; animal model; implants;
D O I
10.1016/j.biopha.2004.08.001
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The use of biodegradable polymers for drug delivery systems excluded the need for a second operation to remove the carrier. However, the development of an avascular fibrous capsule, reducing drug release, has raised concern about these polymers in terms of tissue-implant reaction. Five novel polymers were evaluated in vivo after implantation in the rat dorsal subcutis and compared to the reference polycaprolactone (PCL). Poly(cyclohexyl-sebacate) (PCS), poly (L-lactide-b-1,5-dioxepan-2-one-b-L-lactide) (PLLA-PDXO-PLLA), two 3-hydroxybutyrate-co-3-hydroxyvalerate copolymers (D400G and D600G), and a poly (organo)phosphazene (POS-PheOEt:Imidazole) specimens were histologically evaluated in terms of the inflammatory tissue thickness and vascular density at 4 and 12 weeks from surgery. The highest values of inflammatory tissue thickness were observed in D600G (P < 0.01), PCS (P < 0.001) and PLLA-PDXO-PLLA (P < 0.001) at 4 weeks, while POP-PheOEt:Imidazole showed the lowest value of inflammatory tissue thickness (P < 0.05) at 12 weeks. D400G, D600G, PLLA-PDXO-PPLA and POP-PheOEt:Imidazole showed higher (P < 0.001) values of vascular density near the implants in comparison to PCL at 4 weeks. Finally, D400G and D600G increased their vessel densities while POP-PheOEt:Imidazole and the synthetic polyester PLLA-PDXO-PLLA presented similar vessel density values during experimental times. These different behaviours to improve neoangiogenesis without severe inflammatory tissue-responses could be further investigated with drugs in order to obtain time-programmable drug delivery systems for musculoskeletal therapy. (C) 2004 Elsevier SAS. All rights reserved.
引用
收藏
页码:411 / 417
页数:7
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