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

Research output: Contribution to journalArticle

63 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.
LanguageEnglish
Pages411-417
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume58
Issue number8
DOIs
Publication statusPublished - Oct 2004

Fingerprint

Drug Delivery Systems
Orthopedics
Polymers
Blood Vessels
Polyesters
3-Hydroxybutyric Acid
Capsules
imidazole
Pharmaceutical Preparations
polycaprolactone
Therapeutics

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. / New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation. In: Biomedicine and Pharmacotherapy. 2004 ; Vol. 58, No. 8. pp. 411-417.
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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.",
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Giavaresi, G, Tschon, M, Borsari, V, Daly, JH, Liggat, JJ, 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, vol. 58, no. 8, pp. 411-417. https://doi.org/10.1016/j.biopha.2004.08.001

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

In: Biomedicine and Pharmacotherapy, Vol. 58, No. 8, 10.2004, p. 411-417.

Research output: Contribution to journalArticle

TY - JOUR

T1 - New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation

AU - Giavaresi, G.

AU - Tschon, M.

AU - Borsari, V.

AU - Daly, J.H.

AU - Liggat, J.J.

AU - Fini, M.

AU - Bonazzi, V.

AU - Nicolini, A.

AU - Carpi, A.

AU - Morra, M.

AU - Cassinelli, C.

AU - Giardino, R.

PY - 2004/10

Y1 - 2004/10

N2 - 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.

AB - 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.

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KW - polymers

KW - polyesters

KW - polyphosphazenes

KW - animal model

KW - implants

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