Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer

Liu, Jiang; Meisner, Dale; Kwong, Elizabeth; Wu, Xiao Yu; Johnston, Michael

doi:10.1158/0008-5472.can-08-1753

Cited by 47 publications

(44 citation statements)

References 28 publications

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“…29 To date, studies focusing on the intrapleural delivery of nanomedicine have been very rare, but the results have shown favorable control of lung cancer. 30 The results of the current study may consolidate these published findings and could trigger more research on the intrapleural delivery of nanomedicine for the control of primary or secondary lung cancer.…”

supporting

confidence: 74%

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

Shen¹,

Shyu²,

Lu³

et al. 2015

IJN

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The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil ® , the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future.

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supporting

confidence: 74%

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

Shen¹,

Shyu²,

Lu³

et al. 2015

IJN

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“…Shikanov, et al, injected a semiliquid extended release polymer loaded with Paclitaxel to an orthotopic R3327 rat prostate tumor, which inhibited the prostate tumor and its metastasis to lung and lymph nodes for 25 days [28]. Liu, et al, placed a gelatin sponge with PLGA microspheres containing Paclitaxel near orthotopic rat lung cancer, and found that during a 14 -32 day period, the mediastinum lymph nodes have higher area under the curve AUC drug and fewer metastatic tumors than IV treated tumors [31]. Both of the two studies bear similarities to our report.…”

Section: An Ideal Pharmacological Paradigm Achievablementioning

confidence: 99%

A Totally Absorbable Multilayer PLGA Implant Device Containing Doxorubicin Inhibited Tumor Growth and Metastasis without Systemic Toxicity in Murine Breast Cancer and an Ideal Pharmacological Paradigm for Regional Chemotherapy

Elzey¹,

Torregrosa-Allen²,

Li³

et al. 2016

JBM

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We hypothesize that a cylinder implant made of multilayer Poly-lactic-co-glycolic-acid (PLGA) membrane can be a method for controlled and extended drug release. We fashioned a multilayer cylindrical implant termed STID100 that released doxorubicin for 3 weeks in an orthotopic 4T1 breast cancer model in Balb/C mice. This implant starts as a thin doxorubicin-embedded PLGA membrane, and is then rolled into a cylinder containing an air gap between the membrane layers. Its controlled sustained release delivered 2× the amount of the intravenous (IV) equivalent of doxorubicin, inhibited the primary tumor, and prevented lung metastasis. Importantly it did not cause weight loss, splenomegaly, or cardiac toxicity vs systemically administrated doxorubicin. This favorable safety profile is further substantiated by the finding of no detectable plasma doxorubicin in multiple time points during the 3-week period, and low tumor doxorubicin concentration. The implant system delivered to the specification of an ideal pharmacological paradigm might offer a better coverage of the local tumor, significantly preventing metastatic spread with less drug toxicity to many vital organs, compared to the traditional pharmacology of IV route. The profile of STID made it an attractive therapeutic alternative in metastatic tumor prevention, pain management * Corresponding author. B. Elzey et al. 67and many other diverse clinical scenarios.

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“…Paclitaxel (PTX) is one of the most potent anticancer drugs, and is widely used in the therapy of NSCLC. 9,10 Nevertheless, the clinical use of PTX is limited by poor aqueous solubility, high toxicity, and low bioavailability. 11 Taxol is one of the formulations of PTX that can be used in the therapy of NSCLS.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Zhao¹,

Chen²,

Yan³

et al. 2013

IJN

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Abstract:In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS 2k NPs) was prepared. The novel amphiphilic copolymer (PGA-co-PCL)-b-TPGS 2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL)-b-TPGS 2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL)-b-TPGS 2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL)-b-TPGS 2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.

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Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer

Cited by 47 publications

References 28 publications

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

A Totally Absorbable Multilayer PLGA Implant Device Containing Doxorubicin Inhibited Tumor Growth and Metastasis without Systemic Toxicity in Murine Breast Cancer and an Ideal Pharmacological Paradigm for Regional Chemotherapy

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

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Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer

Cited by 47 publications

References 28 publications

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

A Totally Absorbable Multilayer PLGA Implant Device Containing Doxorubicin Inhibited Tumor Growth and Metastasis without Systemic Toxicity in Murine Breast Cancer and an Ideal Pharmacological Paradigm for Regional Chemotherapy

Paclitaxel-loaded poly(glycolide-co-&epsilon;-caprolactone)-b-D-&alpha;-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

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Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy