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

G. Giavaresi, M. Tschon, V. Borsari, J.H. Daly, J.J. Liggat, M. Fini, V. Bonazzi, A. Nicolini, A. Carpi, M. Morra, C. Cassinelli, R. Giardino

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64 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)411-417
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume58
Issue number8
DOIs
Publication statusPublished - Oct 2004

Keywords

  • drug delivery systems
  • polymers
  • polyesters
  • polyphosphazenes
  • animal model
  • implants

Cite this

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. (2004). New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation. Biomedicine and Pharmacotherapy, 58(8), 411-417. https://doi.org/10.1016/j.biopha.2004.08.001