Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin

Petersen, Grant H.; Alzghari, Saeed K; Chee, Wayne; Sankari, Sana S.; La‐Beck, Ninh M.

doi:10.1016/j.jconrel.2016.04.028

Cited by 249 publications

(143 citation statements)

References 48 publications

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“…Drug delivery using nanoparticle carriers drastically alters the pharmacokinetics and pharmacodynamics of the drug cargo as compared to the conventional non-carrier mediated formulation due to changes in tissue and cellular distribution dictated by the carrier [9]. This has been exploited to improve drug pharmacokinetic parameters ( e.g.…”

Section: Discussionmentioning

confidence: 99%

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Rajan

Sabnani

Mavinkurve

et al. 2018

Journal of Controlled Release

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Liposomal nanoparticles are the most commonly used drug nano-delivery platforms. However, recent reports show that certain pegylated liposomal nanoparticles (PLNs) and polymeric nanoparticles have the potential to enhance tumor growth and inhibit antitumor immunity in murine cancer models. We sought herein to identify the mechanisms and determine whether PLN-associated immunosuppression and tumor growth can be reversed using alendronate, an immune modulatory drug. By conducting in vivo and ex vivo experiments with the immunocompetent TC-1 murine tumor model, we found that macrophages were the primary cells that internalized PLN in the tumor microenvironment and that PLN-induced tumor growth was dependent on macrophages. Treatment with PLN increased immunosuppression as evidenced by increased expression of arginase-1 in CD11b+Gr1+ cells, diminished M1 functionality in macrophages, and globally suppressed T-cell cytokine production. Encapsulating alendronate in PLN reversed these effects on myeloid cells and shifted the profile of multi-cytokine producing T-cells towards an IFNγ+ perforin+ response, suggesting increased cytotoxic functionality. Importantly, we also found that PLN-encapsulated alendronate (PLN-alen), but not free alendronate, abrogated PLN-induced tumor growth and increased progression-free survival. In summary, we have identified a novel mechanism of PLN-induced tumor growth through macrophage polarization and immunosuppression that can be targeted and inactivated to improve the anticancer efficacy of PLN-delivered drugs. Importantly, we also determined that PLN-alen not only reversed protumoral effects of the PLN carrier, but also had moderate antitumor activity. Our findings strongly support the inclusion of immune-responsive tumor models and in-depth immune functional studies in the preclinical drug development paradigm for cancer nanomedicines, and the further development of chemo-immunotherapy strategies to co-deliver alendronate and chemotherapy for the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Rajan

Sabnani

Mavinkurve

et al. 2018

Journal of Controlled Release

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“…In this way, liposomes have, to some extent, the ability to pass in and out of the liver and spleen, avoiding clearance, and thus remain in the tumor tissue due to the depleted lymphatic drainage [24,25]. In previous studies, anticancer agents that were incorporated in PEGylated liposomes displayed longer circulation times and enhanced drug delivery to tumor tissues [26].…”

Section: Introductionmentioning

confidence: 99%

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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Abstract:Liposomes are considered to be one of the most successful drug delivery systems.They apply nanotechnology to potentiate the therapeutic efficacy and reduce the toxicity of conventional medicines. Shikonin and alkannin, a pair of chiral natural naphthoquinone compounds, derived from Alkanna and Lithospermum species, are widely used due to their various pharmacological activities, mainly wound healing, antioxidant, anti-inflammatory and their recently established antitumor activity. The purpose of this study was to prepare conventional and PEGylated shikonin-loaded liposomal formulations and measure the effects of different lipids and polyethylene glycol (PEG) on parameters related to particle size distribution, the polydispersity index, the zeta potential, drug-loading efficiency and the stability of the prepared formulations. Three types of lipids were assessed (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DSPG)), separately and in mixtures, forming anionic liposomes with good physicochemical characteristics, high entrapment efficiencies (varying from 56.5 to 89.4%), satisfactory in vitro release profiles and good physical stability. The addition of the negatively charged DSPG lipids to DOPC, led to an increment in the drug's incorporation efficiency and reduced the particle size distribution. Furthermore, the shikonin-loaded PEGylated sample with DOPC/DSPG, demonstrated the most satisfactory characteristics. These findings are considered promising and could be used for further design and improvement of such formulations.

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“…Furthermore, the progression-free survival and total survival of patients increased when liposomal doxorubicin was used, whereas it showed no significant statistical difference from traditional therapy with doxorubicin. Another meta-analysis suggests that, compared to the animal model, the effect of PLD is not significantly enhanced compared with the traditional doxorubicin, and an optimized dosage regimen and method are still needed (Petersen et al, 2016). With the performance of ongoing clinical studies, different objects may be set for comparison in such analysis, so as to obtain more valuable information, which may be further verified by pertinent clinical studies.…”

Section: Statistical Analysis Based On a Large Number Of Samplesmentioning

confidence: 99%

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

Zhao

Ding

Shen

et al. 2017

J. Zhejiang Univ. Sci. B

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Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for developing anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs. Although liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD) in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.

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Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin

Cited by 249 publications

References 48 publications

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

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