3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine

With the aim of fabricating drug-loaded implantable patches, a 3D printing technique was employed to produce novel coaxial hydrogel patches. The core-section of these patches contained a dopamine-modified methacrylated alginate hydrogel loaded with a chemotherapeutic drug (Gemcitabine), while their...

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Main Authors: Sepehr Talebian, In Kyong Shim, Javad Foroughi, Gorka Orive, Kara L. Vine, Song Cheol Kim, Gordon G. Wallace
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/13/24/4367
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author Sepehr Talebian
In Kyong Shim
Javad Foroughi
Gorka Orive
Kara L. Vine
Song Cheol Kim
Gordon G. Wallace
author_facet Sepehr Talebian
In Kyong Shim
Javad Foroughi
Gorka Orive
Kara L. Vine
Song Cheol Kim
Gordon G. Wallace
author_sort Sepehr Talebian
collection DOAJ
description With the aim of fabricating drug-loaded implantable patches, a 3D printing technique was employed to produce novel coaxial hydrogel patches. The core-section of these patches contained a dopamine-modified methacrylated alginate hydrogel loaded with a chemotherapeutic drug (Gemcitabine), while their shell section was solely comprised of a methacrylated alginate hydrogel. Subsequently, these patches were further modified with CaCO<sub>3</sub> cross linker and a polylactic acid (PLA) coating to facilitate prolonged release of the drug. Consequently, the results showed that addition of CaCO<sub>3</sub> to the formula enhanced the mechanical properties of the patches and significantly reduced their swelling ratio as compared to that for patches without CaCO<sub>3</sub>. Furthermore, addition of PLA coating to CaCO<sub>3</sub>-containing patches has further reduced their swelling ratio, which then significantly slowed down the release of Gemcitabine, to a point where 4-layered patches could release the drug over a period of 7 days in vitro. Remarkably, it was shown that 3-layered and 4-layered Gemcitabine loaded patches were successful in inhibiting pancreatic cancer cell growth for a period of 14 days when tested in vitro. Lastly, in vivo experiments showed that gemcitabine-loaded 4-layered patches were capable of reducing the tumor growth rate and caused no severe toxicity when tested in mice. Altogether, 3D printed hydrogel patches might be used as biocompatible implants for local delivery of drugs to diseased site, to either shrink the tumor or to prevent the tumor recurrence after resection.
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spelling doaj.art-f03b297822b54b4ea431d251febe86722023-11-23T10:15:20ZengMDPI AGPolymers2073-43602021-12-011324436710.3390/polym132443673D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of GemcitabineSepehr Talebian0In Kyong Shim1Javad Foroughi2Gorka Orive3Kara L. Vine4Song Cheol Kim5Gordon G. Wallace6Intelligent Polymer Research Institute, ARC Centre of Excellence for Electromaterials Science, AIIM Facility, University of Wollongong, Wollongong, NSW 2522, AustraliaAsan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaFaculty of Engineering and Information Sciences, University of Wollongong, Wollongong, NSW 2522, AustraliaNanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainIllawarra Health and Medical Research Institute, Wollongong, NSW 2522, AustraliaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2 Dong, Songpa-gu, Seoul 05505, KoreaIntelligent Polymer Research Institute, ARC Centre of Excellence for Electromaterials Science, AIIM Facility, University of Wollongong, Wollongong, NSW 2522, AustraliaWith the aim of fabricating drug-loaded implantable patches, a 3D printing technique was employed to produce novel coaxial hydrogel patches. The core-section of these patches contained a dopamine-modified methacrylated alginate hydrogel loaded with a chemotherapeutic drug (Gemcitabine), while their shell section was solely comprised of a methacrylated alginate hydrogel. Subsequently, these patches were further modified with CaCO<sub>3</sub> cross linker and a polylactic acid (PLA) coating to facilitate prolonged release of the drug. Consequently, the results showed that addition of CaCO<sub>3</sub> to the formula enhanced the mechanical properties of the patches and significantly reduced their swelling ratio as compared to that for patches without CaCO<sub>3</sub>. Furthermore, addition of PLA coating to CaCO<sub>3</sub>-containing patches has further reduced their swelling ratio, which then significantly slowed down the release of Gemcitabine, to a point where 4-layered patches could release the drug over a period of 7 days in vitro. Remarkably, it was shown that 3-layered and 4-layered Gemcitabine loaded patches were successful in inhibiting pancreatic cancer cell growth for a period of 14 days when tested in vitro. Lastly, in vivo experiments showed that gemcitabine-loaded 4-layered patches were capable of reducing the tumor growth rate and caused no severe toxicity when tested in mice. Altogether, 3D printed hydrogel patches might be used as biocompatible implants for local delivery of drugs to diseased site, to either shrink the tumor or to prevent the tumor recurrence after resection.https://www.mdpi.com/2073-4360/13/24/4367hydrogel3D printingdrug deliverycancer
spellingShingle Sepehr Talebian
In Kyong Shim
Javad Foroughi
Gorka Orive
Kara L. Vine
Song Cheol Kim
Gordon G. Wallace
3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine
Polymers
hydrogel
3D printing
drug delivery
cancer
title 3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine
title_full 3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine
title_fullStr 3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine
title_full_unstemmed 3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine
title_short 3D-Printed Coaxial Hydrogel Patches with Mussel-Inspired Elements for Prolonged Release of Gemcitabine
title_sort 3d printed coaxial hydrogel patches with mussel inspired elements for prolonged release of gemcitabine
topic hydrogel
3D printing
drug delivery
cancer
url https://www.mdpi.com/2073-4360/13/24/4367
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