Formulation and optimization of idarubicin thermosensitive liposomes provides ultrafast triggered release at mild hyperthermia and improves tumor response

Lü, Tao; Lokerse, Wouter J.M.; Seynhaeve, Ann L.B.; Koning, Gerben A.; Hagen, Timo L.M. ten

doi:10.1016/j.jconrel.2015.10.056

Cited by 49 publications

(23 citation statements)

References 48 publications

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“…Ultrafast triggered release of drugs within 20 s [ 32 ] and slower release within one week from TSL [ 21 , 33 ] have been reported. TSL with ultrafast triggered release were considered unstable because serious drug leakage was always observed, indicating that most of the drug couldn’t be delivered to the specific target site and that TSL with ultrafast triggered release would have poor effectiveness in the clinic [ 32 ]. On the other hand, TSL with a long release period were also thought undesirable because HT was always conducted within 45 min [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability

Zeng

Yu²,

Yang³

et al. 2016

PLoS ONE

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Oxaliplatin (OXP) was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL) were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure. The purpose of this study was to acquire OXP TSL with rapid release at the triggered temperature and high stability at body temperature and at storage temperatures. A small quantity of poloxamer 188 was introduced into the TSL formulation to stabilize the encapsulated drug. It was shown that the addition of poloxamer 188 had no influence on the TSL characteristics. More than 90% of OXP was released within 10 min at 42°C, and less than 15% was released within 60 min at temperatures below 39°C. TSL were stable at 37°C for 96 h and at 4°C for 6 months. The anti-tumor activity of TSL at the dose of 2.5 mg/kg was certified to be equal to those of OXP injection and non-thermosensitive liposomes (NTSL) at the dose of 5 mg/kg, and significant improvement of tumor inhibition was observed in TSL compared with injection and NTSL at the same dose. It was also shown from the histological transmutation of tumors that TSL had stronger anti-tumor activity. Therefore, it could be concluded that TSL composed of a proper amount of poloxamer had rapid release and high stability, and OXP TSL would be anticipated to exert prominent anti-tumor activity in the clinic.

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Section: Resultsmentioning

confidence: 99%

Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability

Zeng

Yu²,

Yang³

et al. 2016

PLoS ONE

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“…The initial studies with daunorubicin in the mid-1990s in mice models of sarcoma were disappointing [51]. However, more recent studies with newer formulations of idarubicin-TSL showed superior survival rate and tumor growth inhibition as compared to free idarubicin [52]. Similar results were demonstrated with epirubicin-TSL in animals [53].…”

Section: Payloadsmentioning

confidence: 77%

Thermosensitive Liposomes

Motamarry¹,

Asemani²,

Haemmerich³

2017

Liposomes

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Thermosensitive liposomes (TSLs) are a drug delivery system for targeted delivery that release the encapsulated drug when heated to fever temperatures (∼40-42°C). Combined with localized hyperthermia, TSLs allow precise drug delivery to a targeted region. While mostly investigated as cancer therapy, other applications including treatment of local infections and wound healing have been explored. Over the last ∼40 years, numerous TSL formulations and payloads have been investigated. As with other nanoparticles, the addition of targeting molecules to TSL has been examined to improve targeted delivery. TSL release kinetics and plasma stability are two important factors that affect efficacy, and new formulations often aim to further improve on these properties. The possibility of encapsulating a magnetic resonance (MR) contrast agent that is released together with the encapsulated drug allows for visualization of drug delivery with MR imaging. Various heating modalities have been examined in combination with TSL. Since the goal is to expose a defined tissue region to uniform temperatures within the range where TSLs release (typically ∼40-43°C), the choice of an appropriate heating modality has considerable impact on treatment efficacy. Several ongoing clinical trials with TSL as cancer therapy suggest the potential for clinical impact in the near future. Figure 1. Current drug targeting strategies. (A) Conventional therapy or free drug infusion. (B) Passive targeting by liposomes utilizing EPR effect. (C) Active targeting of liposomes labeled with tumor-specific antibody. (D) Active targeting of liposomes with endothelial cell-specific antibody. (E) Triggered drug release either (1) within the tumor interstitium or (2) intravascular release. TSL fall into this last category reproduced with permission from Ref. [1].

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“…[26]. For example, Idarubicin (IDA), a drug exclusively used for the treatment of leukemia through thermosensitive liposomes (TSL) in combination with hyperthermia (HT) demonstrated to be more prominent tumor growth inhibition in leukemia than in the conventional form [27].…”

Section: Liposomes Drug Delivery In Cancermentioning

confidence: 99%