Pharmacological basis of pegylated liposomal doxorubicin: Impact on cancer therapy

Gabizón, Alberto; Shmeeda, Hilary; Grenader, Tal

doi:10.1016/j.ejps.2011.09.006

Cited by 99 publications

(69 citation statements)

References 73 publications

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“…One explanation for the superior antitumoral effect of LPDP-M could be a specific pharmacokinetic interference between nab-paclitaxel and liposomal doxorubicin. For non-modified paclitaxel, an inhibitory effect has been described specifically on liposomal doxorubicin, resulting in further prolongation of plasma half-life and enhanced therapeutic efficacy (Gabizon et al 2011). We cannot exclude the possibility that this observation might also be relevant for the albumin-bound form of paclitaxel.…”

Section: Discussionmentioning

confidence: 82%

“…This enhanced antitumor efficacy in comparison with the free drugs can be explained by the previously described general advantages mediated by sterically stabilized liposomes including slower drug release rates, increased plasma half-life, and passive drug accumulation of liposomes (Immordino et al 2006, Gabizon et al 2011. Furthermore, the active uptake of liposomes by ACC cells could have further contributed to this finding (Hantel et al 2012).…”

Section: Discussionmentioning

confidence: 84%

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Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

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Owing to high relapse rates and early metastatic spread, prognosis in adrenocortical carcinoma (ACC) patients remains poor, highlighting the importance of developing new treatment alternatives for them. Recently, polychemotherapy regimens including etoposide, doxorubicin, and cisplatin together with mitotane (EDP-M) have been defined as the standard treatment for late-stage disease patients. Nevertheless, the administration of conventional cytostatic drugs is associated with severe and dose-limiting side effects. In an attempt to optimize existing clinical treatment regimens, in this study, we investigated the therapeutic efficacy of EDP-M in comparison with that of a paclitaxel-modified scheme (paclitaxel, doxorubicin, cisplatin plus mitotane (PDP-M)) in preclinical in vitro and in vivo models. In addition, based on an extraordinary uptake phenomenon of liposomes in ACC cells, we further evaluated liposomal variants of these protocols (etoposide, liposomal doxorubicin, liposomal cisplatin plus mitotane (LEDP-M) and nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin plus mitotane (LPDP-M)). In vitro, PDP-M was more potent in the induction of apoptosis and inhibition of cell viability as well as cell proliferation than EDP-M. Following the administration of a single therapeutic cycle, we further demonstrated that LEDP-M and LPDP-M exerted significant antitumoral effects in vivo, which were not as evident upon EDP-M and PDP-M treatments. These results were confirmed in a long-term experiment, in which the highest and sustained antitumoral effects were observed for LEDP-M. In summary, liposomal cytostatic substances could represent a promising option that deserves testing in appropriate clinical protocols for the treatment of ACC patients.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 84%

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

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“…Liposomal drug delivery to tumor deposits benefits from the "enhanced permeability and retention effect," whereby preferential extravasation of these particles occurs across hyperpermeable tumor-associated blood vessels (29). Local drug concentrations are further enhanced owing to the lack of effective lymphatic drainage within tumors, creating a reservoir of the therapeutic agent at the site of disease (30,31). Clinical exploitation of this principle offers the promise that cytotoxic activity of gd T cells would be targeted more precisely to tumor deposits, rather than healthy tissue, following infusion into the peritoneal cavity.…”

Section: Discussionmentioning

confidence: 99%

Adoptive Immunotherapy of Epithelial Ovarian Cancer with Vγ9Vδ2 T Cells, Potentiated by Liposomal Alendronic Acid

Parente-Pereira

Shmeeda

Whilding

et al. 2014

The Journal of Immunology

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Adoptive immunotherapy using γδ T cells harnesses their natural role in tumor immunosurveillance. The efficacy of this approach is enhanced by aminobisphosphonates such as zoledronic acid and alendronic acid, both of which promote the accumulation of stimulatory phosphoantigens in target cells. However, the inefficient and nonselective uptake of these agents by tumor cells compromises the effective clinical exploitation of this principle. To overcome this, we have encapsulated aminobisphosphonates within liposomes. Expanded Vγ9Vδ2 T cells from patients and healthy donors displayed similar phenotype and destroyed autologous and immortalized ovarian tumor cells, following earlier pulsing with either free or liposome-encapsulated aminobisphosphonates. However, liposomal zoledronic acid proved highly toxic to SCID Beige mice. By contrast, the maximum tolerated dose of liposomal alendronic acid was 150-fold higher, rendering it much more suited to in vivo use. When injected into the peritoneal cavity, free and liposomal alendronic acid were both highly effective as sensitizing agents, enabling infused γδ T cells to promote the regression of established ovarian tumors by over one order of magnitude. Importantly however, liposomal alendronic acid proved markedly superior compared with free drug following i.v. delivery, exploiting the “enhanced permeability and retention effect” to render advanced tumors susceptible to γδ T cell–mediated shrinkage. Although folate targeting of liposomes enhanced the sensitization of folate receptor–α+ ovarian tumor cells in vitro, this did not confer further therapeutic advantage in vivo. These findings support the development of an immunotherapeutic approach for ovarian and other tumors in which adoptively infused γδ T cells are targeted using liposomal alendronic acid.

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“…In vitro use of these drugs in combination protocols was reported for sclareol and methotrexate, 27,28 in vivo for paclitaxel, cisplatin and dexamethasone; 8,[29][30][31] and with patients for doxorubicin, paclitaxel, mitoxantrone and methotrexate. [16][17][18][32][33][34] Their sequential combination with doxorubicin in a spheroid model was studied in this report. In addition, we used doxorubicin in its free, micellar and liposomal form, which allowed us to compare the permeability of spheroids for different drug formulations.…”

Section: Introductionmentioning

confidence: 99%

Cancer cell spheroids as a model to evaluate chemotherapy protocols

Perche

Torchilin

2012

Cancer Biology & Therapy

126

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Pharmacological basis of pegylated liposomal doxorubicin: Impact on cancer therapy

Cited by 99 publications

References 73 publications

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Adoptive Immunotherapy of Epithelial Ovarian Cancer with Vγ9Vδ2 T Cells, Potentiated by Liposomal Alendronic Acid

Cancer cell spheroids as a model to evaluate chemotherapy protocols

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