Studies have demonstrated the advantages associated with heat-triggered drug delivery via thermosensitive liposomes for the treatment of localized cancer. Challenges that traditional liposomal systems face such as limited drug release and homogeneous distribution throughout the region of interest can potentially be overcome when triggering intravascular drug release. The most prominent example is a thermosensitive liposome formulation of doxorubicin known as ThermoDox®. Many other drugs may benefit from the same targeted and localized delivery approach using thermosensitive liposomes as it can result in a significant improvement in the therapeutic index. Vinorelbine is a semi-synthetic vinca alkaloid which has shown to be active in a broad range of cancers. Several liposome formulations encapsulating vinorelbine have been developed as a means to reduce systemic drug exposure. The present study takes a systematic approach in exploring formulation and drug loading parameters and their influence on performance characteristics of a rapidly releasing thermosensitive liposome formulation of vinorelbine. More broadly, this study shows that trends observed for non-thermosensitive liposome formulations of specific drugs (i.e. vinorelbine) can not be easily translated to their thermosensitive counterparts. The profound impact of the presence of albumin on stability and in vitro release is also highlighted. This is of significance given that a number of recent reports examine drug release in the absence of biologically relevant components. As a result, a strong recommendation emanating from this is a thorough challenge of the liposome formulation in vitro in order to gain a better understanding of its likely behaviour in vivo as well as potential for future clinical translation.

Determining critical parameters that influence in vitro performance characteristics of a thermosensitive liposome formulation of vinorelbine

Casettari, Luca;
2020-01-01

Abstract

Studies have demonstrated the advantages associated with heat-triggered drug delivery via thermosensitive liposomes for the treatment of localized cancer. Challenges that traditional liposomal systems face such as limited drug release and homogeneous distribution throughout the region of interest can potentially be overcome when triggering intravascular drug release. The most prominent example is a thermosensitive liposome formulation of doxorubicin known as ThermoDox®. Many other drugs may benefit from the same targeted and localized delivery approach using thermosensitive liposomes as it can result in a significant improvement in the therapeutic index. Vinorelbine is a semi-synthetic vinca alkaloid which has shown to be active in a broad range of cancers. Several liposome formulations encapsulating vinorelbine have been developed as a means to reduce systemic drug exposure. The present study takes a systematic approach in exploring formulation and drug loading parameters and their influence on performance characteristics of a rapidly releasing thermosensitive liposome formulation of vinorelbine. More broadly, this study shows that trends observed for non-thermosensitive liposome formulations of specific drugs (i.e. vinorelbine) can not be easily translated to their thermosensitive counterparts. The profound impact of the presence of albumin on stability and in vitro release is also highlighted. This is of significance given that a number of recent reports examine drug release in the absence of biologically relevant components. As a result, a strong recommendation emanating from this is a thorough challenge of the liposome formulation in vitro in order to gain a better understanding of its likely behaviour in vivo as well as potential for future clinical translation.
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/11576/2679936
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact