Poly-hydroxy-aspartamide was used as a backbone to synthesize bisphosphonate derivatives thus achieving macromolecular carriers to be potentially used as targeting agents for bone drug delivery. Molecules bearing bisphosphonate groups, such as aminobisphosphonate (ABP) and neridronate (NRD), have been conjugated to polyaspartamide (alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide, PHEA), with or without a spacer (succinic acid or 6-aminocaproic acid) thus obtaining PHEA-succinate-ABP and PHEA-caproylcarbamate-ABP and PHEA-ABP and PHEA-NRD, respectively. Bisphosphonate-polymer conjugates were physico-chemically characterized using size exclusion chromatography and H-1-NMR; and their in vitro and ex vivo affinity for bone tissue has been further tested using the hydroxylapatite and rabbit bone binding assays, respectively. In vivo studies were carried out using rats to evaluate the biodistribution features of bisphosphonate-polymer conjugates in comparison with the starting PHEA. In vivo findings evidenced a suitable selectivity of bisphosphonate-polymer conjugates toward the bone tissues also as a function of time.

Bisphosphonate-polyaspartamide conjugates as bone targeted drug delivery systems

Paolino D;Fresta M;
2015-01-01

Abstract

Poly-hydroxy-aspartamide was used as a backbone to synthesize bisphosphonate derivatives thus achieving macromolecular carriers to be potentially used as targeting agents for bone drug delivery. Molecules bearing bisphosphonate groups, such as aminobisphosphonate (ABP) and neridronate (NRD), have been conjugated to polyaspartamide (alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide, PHEA), with or without a spacer (succinic acid or 6-aminocaproic acid) thus obtaining PHEA-succinate-ABP and PHEA-caproylcarbamate-ABP and PHEA-ABP and PHEA-NRD, respectively. Bisphosphonate-polymer conjugates were physico-chemically characterized using size exclusion chromatography and H-1-NMR; and their in vitro and ex vivo affinity for bone tissue has been further tested using the hydroxylapatite and rabbit bone binding assays, respectively. In vivo studies were carried out using rats to evaluate the biodistribution features of bisphosphonate-polymer conjugates in comparison with the starting PHEA. In vivo findings evidenced a suitable selectivity of bisphosphonate-polymer conjugates toward the bone tissues also as a function of time.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/5462
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 28
  • ???jsp.display-item.citation.isi??? 24
social impact