Abstract
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 CaCO3 cross linker and a polylactic acid (PLA) coating to facilitate prolonged release of the drug. Consequently, the results showed that addition of CaCO3 to the formula enhanced the mechanical properties of the patches and significantly reduced their swelling ratio as compared to that for patches without CaCO3. Furthermore, addition of PLA coating to CaCO3-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.
Highlights
The therapeutic approaches for cancer are very much dependent on the type and state of the disease, and a variety of treatments have been exploited in the clinic setting to date [1]
The results showed that these scaffolds were capable of releasing DOX over a period of 14 days and, when tested in mice with subcutaneous MDA-MB-231 breast cancer tumors, they were capable of inhibiting tumor growth to a higher degree with less systemic toxicity compared to that of mice who received equivalent dosage of the drug systemically [13]
These results showed that empty patches did not cause any significant toxicity to the cells, but long-term therapeutic effects of these drug loaded patches is essential to evaluate their potential in preventing the cancer cell growth
Summary
The therapeutic approaches for cancer are very much dependent on the type and state of the disease, and a variety of treatments have been exploited in the clinic setting to date [1]. It was shown that the specific geometry (latticed, slant, or triangular) and number of layers could directly affect the release profile of 5-FU These patches could release 5-FU over a period of 4 weeks and, when tested in mice with subcutaneous MIA-PaCa-2 pancreatic tumors, they induced significant reduction in relative tumor size compared to that of empty implanted patches. In another instance, 3D printed scaffolds made from PCL were used for local delivery of Doxorubicin (DOX) to inhibit breast cancer tumor growth [13]. 3D-printed hydrogel patches has been shown to be effective, and with future development, these patches might become useful as neo-adjuvant or adjuvant therapies in cancer patients
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