Giavaresi G, Tschon M, Borsari V, Daly J H, Liggat J J, Fini M, Bonazzi V, Nicolini A, Carpi A, Morra M, Cassinelli C, Giardino R
Department of Experimental Surgery, Istituti Ortopedici Rizzoli, Via di Barbiano, 1/10, 40136 Bologna, Italy.
Biomed Pharmacother. 2004 Oct;58(8):411-7. doi: 10.1016/j.biopha.2004.08.001.
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.
将可生物降解聚合物用于药物递送系统无需进行二次手术来移除载体。然而，无血管纤维囊的形成会降低药物释放，这引发了人们对这些聚合物在组织植入反应方面的担忧。将五种新型聚合物植入大鼠背部皮下进行体内评估，并与参比聚己内酯（PCL）进行比较。对聚（环己基癸二酸酯）（PCS）、聚（L-丙交酯-b-1,5-二氧杂环庚烷-2-酮-b-L-丙交酯）（PLLA-PDXO-PLLA）、两种3-羟基丁酸-co-3-羟基戊酸共聚物（D400G和D600G）以及一种聚（有机）磷腈（POS-PheOEt:咪唑）标本，在术后4周和12周从组织学角度评估炎症组织厚度和血管密度。在4周时，D600G（P < 0.01）、PCS（P < 0.001）和PLLA-PDXO-PLLA（P < 0.001）的炎症组织厚度值最高，而在12周时，POP-PheOEt:咪唑的炎症组织厚度值最低（P < 0.05）。在4周时，与PCL相比，D400G、D600G、PLLA-PDXO-PPLA和POP-PheOEt:咪唑在植入物附近的血管密度值更高（P < 0.001）。最后，D400G和D600G的血管密度增加，而在实验期间，POP-PheOEt:咪唑和合成聚酯PLLA-PDXO-PLLA呈现出相似的血管密度值。为了获得用于肌肉骨骼治疗的时间可编程药物递送系统，这些在不引发严重炎症组织反应的情况下改善新生血管形成的不同行为可以进一步与药物进行研究。
