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 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.
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, Republic of Korea.
Hee-Gyeong
HG
Yi
Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang, Kyungbuk, Republic of Korea.
Yeong-Jin
YJ
Choi
Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Kyung Shin
KS
Kang
Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Jung Min
JM
Hong
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, Republic of Korea.
Ruby Gupta
RG
Pati
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, Republic of Korea.
Moon Nyeo
MN
Park
Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
In Kyong
IK
Shim
Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Chan Mi
CM
Lee
Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; Department of Surgery, University of Ulsan Colleague of Medicine & Asan Medical Center, Seoul, Republic of Korea. Electronic address: drksc@amc.seoul.kr.
Song Cheol
SC
Kim
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, Republic of Korea. Electronic address: dwcho@postech.ac.kr.
Dong-Woo
DW
Cho
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011091:Polyesters / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry*; D066330:Printing, Three-Dimensional / Q000295:instrumentation
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; D011098:Polyglactin 910; D005472:Fluorouracil
3D printing; Biodegradable patch; Local drug delivery; Pancreatic cancer