A 3D-printed local drug delivery patch for pancreatic cancer growth suppression

Since recurrence and metastasis of pancreatic cancer has a worse prognosis, chemotherapy has been typically performed to attack the remained malignant cells after resection. However, it is difficult to achieve the therapeutic concentration at the tumor site with systemic chemotherapy. Numerous local...

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Bibliographic Details
Published in:Journal of controlled release 2016-09, Vol.238, p.231-241
Main Authors: Yi, Hee-Gyeong, Choi, Yeong-Jin, Kang, Kyung Shin, Hong, Jung Min, Pati, Ruby Gupta, Park, Moon Nyeo, Shim, In Kyong, Lee, Chan Mi, Kim, Song Cheol, Cho, Dong-Woo
Format: Article
Language:English
Subjects:
3D printing
Animals
Antimetabolites, Antineoplastic - administration & dosage
Antimetabolites, Antineoplastic - therapeutic use
Biodegradable patch
Cell Line, Tumor
Delayed-Action Preparations - chemistry
Drug Delivery Systems - instrumentation
Equipment Design
Fluorouracil - administration & dosage
Fluorouracil - therapeutic use
Humans
Local drug delivery
Male
Mice
Mice, Inbred BALB C
Pancreas - drug effects
Pancreas - pathology
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - pathology
Polyesters - chemistry
Polyglactin 910 - chemistry
Printing, Three-Dimensional - instrumentation
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Summary:Since recurrence and metastasis of pancreatic cancer has a worse prognosis, chemotherapy has been typically performed to attack the remained malignant cells after resection. However, it is difficult to achieve the therapeutic concentration at the tumor site with systemic chemotherapy. Numerous local drug delivery systems have been studied to overcome the shortcomings of systemic delivery. However, because most systems involve dissolution of the drug within the carrier, the concentration of the drug is limited to the saturation solubility, and consequently cannot reach the sufficient drug dose. Therefore, we hypothesized that 3D printing of a biodegradable patch incorporated with a high drug concentration would provide a versatile shape to be administered at the exact tumor site as well as an appropriate therapeutic drug concentration with a controlled release. Here, we introduce the 3D-printed patches composed of a blend of poly(lactide-co-glycolide), polycaprolactone, and 5-fluorouracil for delivering the anti-cancer drug in a prolonged controlled manner and therapeutic dose. 3D printing technology can manipulate the geometry of the patch and the drug release kinetics. The patches were flexible, and released the drug over four weeks, and thereby suppressed growth of the subcutaneous pancreatic cancer xenografts in mice with minimized side effects. Our approach reveals that 3D printing of bioabsorbable implants containing anti-cancer drugs could be a powerful method for an effective local delivery of chemotherapeutic agents to treatment of cancers. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2016.06.015