Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system

Fukumura, Ryoichi; Sukhbaatar, Ariunbuyan; Mishra, Radhika; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

doi:10.1111/cas.14867

Cited by 13 publications

(27 citation statements)

References 26 publications

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“…As shown in a previous study, we found that the optimal ranges of osmotic pressure were greater than for saline and <3,000 kPa. 36 The optimal conditions of osmotic pressure and viscosity presented in this study were not limited to DTX. In the LDDS, a solvent with an osmotic pressure and viscosity of 1,960 kPa and 12 mPa·s would be appropriate.…”

Section: Discussionmentioning

confidence: 97%

“…32,33 Preliminary studies have shown that physicochemical ranges were determined by two independent factors: osmotic pressure and viscosity for LDDS. 36 In the present study, we hypothesized that when a chemotherapeutic agent solution with high osmotic pressure and viscosity was given through the LDDS, expansion of lymphatic vessels and sinuses, drug retention, and the subsequent antitumor effect could be controlled. When tumor cells proliferate in the lymphatic sinuses, tumor embolism occurs in the lymphatic sinuses.…”

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confidence: 96%

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Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

2022

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Lymph node (LN) metastasis is one of the most salient prognostic factors for many types of cancer. Despite recent advances in the treatment of metastasis, the 5-year survival rate of patients remains poor, particularly for head and neck cancer, with average 5-year survival rates of approximately 77%, 52%, and 35% for patients with local, regional LN, and distant sites exhibiting metastases, respectively. Thus, the prognosis is worse for patients with LN metastases than for those patients with only localized tumors. 1,2 Survival rates depend on the stage of the cancer metastasis and are mostly correlated with the numbers of LN containing metastases. Therefore, controlling the regional LN is extremely important. Intravenous (i.v.) administration of chemotherapeutic agents is widely used for the treatment of metastatic LN. Most small molecule drugs (<10 nm) have poor aqueous solubility, low bioavailability, and little tissue selectivity. 3 In addition,

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 96%

Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

2022

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“…The LDDS is a local treatment method in which anticancer drugs are injected directly into LNs to target early metastases. 14 , 15 , 16 The LDDS produces a higher drug retention rate and tissue selectivity in LNs compared to systemic chemotherapy and elicits greater antitumor effects. 14 , 16 Assuming clinical application, the amount of drug used is extremely low (1/1000–10,000 of systemic chemotherapy), and side‐effects are minimal.…”

Section: Introductionmentioning

confidence: 99%

“… 14 , 15 , 16 The LDDS produces a higher drug retention rate and tissue selectivity in LNs compared to systemic chemotherapy and elicits greater antitumor effects. 14 , 16 Assuming clinical application, the amount of drug used is extremely low (1/1000–10,000 of systemic chemotherapy), and side‐effects are minimal. Recently, it has been shown that the antitumor effect can be further enhanced by adjusting the anticancer drugs used in LDDS with a highly osmotic, highly viscous solvent.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model

et al. 2022

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Chemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. An LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, total body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis into the proper axillary LN (PALN) and lung in a mouse model. TBI was carried out on day 4 after inoculation using a gamma irradiator. Lymphatic drug delivery into the accessory axillary LN was used to treat PALN. In vivo bioluminescence imaging, high‐frequency ultrasound, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT‐PCR of spleens after combination therapy revealed increased expression of CD4 , CD8 , and IL‐12b , indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.

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“…This often results in insufficient dosage accumulation and retention of the anti-cancer agents required to treat metastasis effectively. In addressing this issue, our group reported a more efficient method for anti-cancer drug delivery to metastatic sites via the lymphatic route [24,29,30]. This delivery route has motivated the design of new nanocomposite-based therapeutic approaches as alternatives to invasive treatment protocols [31,32].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System

et al. 2021

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Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies.

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Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system

Cited by 13 publications

References 26 publications

Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model

The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System

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