Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer

Pokorný, Richard; Wrightson, William R.; Lewis, Robert K.; Paris, Kristie J.; Hofmeister, Arnd; LaRocca, Renato; Myers, Steven R.; Ackerman, Douglas; Galandiuk, Susan

doi:10.1007/bf02070704

Cited by 7 publications

(4 citation statements)

References 14 publications

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“… 12 , 13 Numerous studies have shown that the colon suppository administration of 5FU appeared to be efficient and showed pharmacokinetics similar to that of intravenous administration, but with decreased systemic side effects and increased rectal tissue drug concentration. 14 – 19 Some animal studies demonstrated that administration of 5FU emulsion in the rectal mucous improved drug accumulation in regional lymph nodes, suggesting that 5FU emulsion therapy might be of potential in treating lymph node metastasis from rectal cancer. 20 , 21 However, the solid form, ie, suppositories, was confined to limited drug contact area with the lesion and poor drug permeability crossing rectal mucous membrane.…”

Section: Introductionmentioning

confidence: 99%

In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

Wang

Huang

Guo

et al. 2016

DDDT

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In situ administration of 5-fluorouracil (5FU) “thermosensitive” gel effectively reduced systemic side effects in treating colon rectal cancer; however, the penetration efficacy of the formulation was considerably low due to the poor lipid solubility of 5FU. The aim of this study was to develop thermosensitive gel-mediated 5FU water-in-oil microemulsion (TG-5FU-ME) for improving the infiltration of 5FU. An in vitro release test showed that TG-5FU-ME sustained the drug’s release up to 10 hours. TG-5FU-ME exhibited good stability, and the microemulsion entrapped did not show any change in morphology and 5FU content during the 4-month storage. Transportation test in the Caco-2 cell monolayer showed that TG-5FU-ME had a permeability 6.3 times higher than that of 5FU thermosensitive gel, and the intracellular uptake of 5FU increased by 5.4-fold compared to that of 5FU thermosensitive gel. In vivo tissue distribution analysis exhibited that the TG-5FU-ME group had drug levels in rectal tissue and mesenteric lymph nodes, which were significantly higher than those of 5FU thermosensitive gel group, with very low blood levels of 5FU in both groups. Furthermore, TG-5FU-ME was not associated with detectable morphological damage to the rectal tissue. Conclusively, TG-5FU-ME might be an efficient rectal delivery system to treat colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

Wang

Huang

Guo

et al. 2016

DDDT

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“…Treatment of neoplastic diseases should be aimed at restoring the protective functions of the immune system, and not just at combating the cancer cells themselves. Otherwise, relapse of tumor diseases is inevitable even after the seemingly "successful" treatment [14] .…”

Section: Discussionmentioning

confidence: 99%

Rectal methods of delivery of medical drugs with a protein nature in the therapies of tumor disease

Ukibayev¹,

Datkhayev²,

Myrzakozha³

et al. 2021

J Adv Pharm Educ Res

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“…The dose of 5-FU was selected based on the previous other studies. 6,7) In the case of subcutaneous tumors, mice were first administered with 5-FU either orally or via rectal suppository when tumor volume reached about 200 mm 3 , and thereafter every 3rd day. Glutamic Oxaloacetic Transaminase/Glutamic Pyruvic Transaminase (GOT/GPT) Assay GOT/GPT levels were measured by using a Serum Transaminase assay kit (Asan Pharm, Seoul, Korea) which is based on the Reitman-Frankel method.…”

Section: Dissolution Testmentioning

confidence: 99%

“…7) A conventional rectal suppository such as a suppository formulated with a polyethylene glycol base, which may soften or melt slowly in the site of application due to its relatively high melting point, cannot be rapidly absorbed in the mucous membranes of the absorption site. 8,9) Furthermore, conventional suppositories, which may reach to the end of the canal of the application site, because of its poor mucoadhesive properties, lose drugs at that level, and may also allow the carried drugs to undergo the first-pass effect.…”

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confidence: 99%

Poloxamer 188 and Propylene Glycol-Based Rectal Suppository Enhances Anticancer Effect of 5-Fluorouracil in Mice

Paek

Xuan

Choi

et al. 2006

Biological & Pharmaceutical Bulletin

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Colorectal cancer is among the most common human malignancies, and remains a leading cause of cancer-related morbidity and mortality. Patients with rectal cancer, despite surgery, still have a significant probability of relapse and cancer-related death. Adjuvant treatment is a rapidly evolving field of rectal cancer treatment. The standard approach is a combination of chemotherapy and radiation therapy (RT). The combined chemotherapy and RT for rectal cancer has been shown to increase the proportion of patients cured of their disease.1,2) 5-Fluorouracil (5-FU) has been widely used in the treatment of solid malignancies.3,4) 5-FU administered via suppository has shown less systemic toxicity, while permitting direct topical contact to rectal cancer and higher rectal tissue concentrations than intravenous administration. 5,6) 5-FU is also used as an adjuvant chemotherapeutic agent for rectal cancers.1) It has also been reported that 5-FU suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration. 7)A conventional rectal suppository such as a suppository formulated with a polyethylene glycol base, which may soften or melt slowly in the site of application due to its relatively high melting point, cannot be rapidly absorbed in the mucous membranes of the absorption site. 8,9) Furthermore, conventional suppositories, which may reach to the end of the canal of the application site, because of its poor mucoadhesive properties, lose drugs at that level, and may also allow the carried drugs to undergo the first-pass effect.10) To solve these problems associated with the use of conventional solid suppository, it would be desirable to develop a novel solid suppository, which was a solid phase at room temperature and instantly melted at physiological temperature, and had mucoadhesive properties to such level that it would attach to the site of application, i.e. the rectal mucous membranes. 11)Recently, we have established the mixture composed of poloxamer 188 (P188) and propylene glycol (PG) for suppository having the suitable melting point (30-37°C) and mucoadhesive property. 12)Thus, the purpose of this study is to investigate whether the solid suppository with P188 and PG is a candidate of rectal dosage form for 5-FU in treating not only rectal cancers but skin cancers in mice. MATERIALS AND METHODS MaterialsThe murine CT-26 colon carcinoma cell line was purchased from Korean Cell Line Bank (Seoul, Korea). Fetal bovine serum (FBS) was purchased from GIBCO (Grand Island, NY, U.S.A.). 5-FU was provided by Dong-A Chemical (Seoul, South Korea). P188 which is a copolymer of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) with the ratio of POE/POP of 80/20 and the molecular weight of 8350 was obtained from BF Goodrich (Breesville, OH, U.S.A.), and PG was from DC Chemical Co., Ltd. (Seoul, South Korea). Propylene glycol was of USP grade. The semipermeable membrane tube (Spectra membrane tubing No. 1) was from Spectrum Medical Industries Inc. (Los Angele...

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Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer

Abstract: 5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.

Cited by 7 publications

References 14 publications

In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

Rectal methods of delivery of medical drugs with a protein nature in the therapies of tumor disease

Poloxamer 188 and Propylene Glycol-Based Rectal Suppository Enhances Anticancer Effect of 5-Fluorouracil in Mice

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