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3D Printed Medicine Uses Fish Gelatin to Deliver Cancer Treatment

Japanese researchers Jin Liu, Tatsuaki Tagami, and Tetsuya Ozeki have completed a recent study in nanomedicine, releasing their findings in “Fabrication of 3D Printed Fish-Gelatin-Based Polymer Hydrogel Patches for Local Delivery of PEGylated Liposomal Doxorubicin.” Experimenting with a new drug delivery system, the authors report on new potential for patient-specific cancer treatment.

The study of materials science continues to expand in a wide range of applications; however, bioprinting is one of the most exciting techniques as tissue engineering is expected to lead to the fabrication of human organs in the next decade or so. Such research has also proven that bioprinting may yield much more powerful drug delivery whether in using hybrid systems, multi-drug delivery systems, or improved scaffolds.

Here, the materials chosen for drug delivery are more unique as the researchers combined printer ink with semi-synthesized fish gelatin methacryloyl (F-GelMA)—a cold fish gelatin derivative.

In providing aggressive cancer treatment to patients, the use of doxorubicin (DOX) is common as an anti-carcinogen for the treatment of the following diseases:

  • Breast cancer
  • Bladder cancer
  • Kaposi’s sarcoma
  • Lymphoma
  • Acute lymphocytic leukemia

DOX may also cause serious cardiotoxicity, however, despite its use as a broad-spectrum drug. As a solution, PEGylated liposomal DOX, Doxil has been in use for treatment of cancer with much lower cardiotoxity. The nanomedicine has also been approved by the FDA, and is used for targeting local tumors; for instance, this type of drug delivery system could be suitable for treating a brain tumor.

“PEGylating liposomes can prolong their circulation time in blood, resulting in their passive accumulation in cancer tissue, called the enhanced permeability and retention effect,” state the authors.

Using a 3D bioprinter, the authors developed liposomal patches to be directly implanted into cancerous cells.

(a) Synthesis of fish gelatin methacryloyl (F-GelMA). (b) Hybrid gel of cross-linked F-GelMA and carboxymethyl cellulose sodium (CMC) containing PEGylated liposome. The reaction scheme was prepared in previous studies

“We used a hydrogel containing semi-synthetic fish-gelatin polymer (fish gelatin methacryloyl, F-GelMA) to entrap DOX-loaded PEGylated liposomes. Fish gelatin is inexpensive and faces few personal or religious restrictions,” stated the authors.

Fish gelatin has not been used widely in bioprinting, however, due to low viscosity and rapid polymerization. To solve that problem, the authors created a bioink composite with elevated viscosity.

Viscous properties of drug formulations used as printer inks. (a) The appearance of F-GelMA hydrogels containing different concentrations of CMC. (b) The viscosity profiles of F-GelMA hydrogels containing different concentrations of CMC. The data represent the mean ± SD (n = 3).

And while hydrogels are generally attractive for use due to their ability to swell, for this study, the researchers fabricated a variety of different materials—with the combination of 10% F-GelMA and 7% carboxymethyl cellulose sodium (a thickening agent) showing the highest swelling ratio.

Swelling properties of hydrogels after photopolymerization. (a) Swelling ratio of different concentrations of F-GelMA. (b) Swelling ratio of mixed hydrogel (10% F-GelMA with different concentrations of CMC). The data represent the mean ± SD (n = 3).

Design of the different 3D geometries: (a) cylinder, (b) torus, and (c) gridlines.

Patches were printed in three different sample shapes, using a CELLINK bioprinter syringe as the authors tested drug release potential in vivo. Realizing that surface area, crosslinks density, temperature, and shaker speed would play a role, the team relied on a larger surface volume for more rapid release of drugs.

Printing conditions of patches.

While experimenting with the torus, gridline, and cylindrical sample patches, the researchers observed gridline-style patches as offering the greatest potential for sustained release.

Drug release profiles of liposomal doxorubicin (DOX). (a) Influence of shape on drug release. The UV exposure time was set to 1 min. (b) Influence of UV exposure time on drug release. The gridline object was used for this experiment. The data represent the mean ± SD (n = 3).

“These results indicate that CMC is useful for adjusting the properties of printer ink and is a useful and safe pharmaceutical excipient in drug formulations. We also showed that drug release from 3D-printed patches was dependent on the patch shapes and UV exposure time, and that drug release can be controlled. Taken together, the present results provide useful information for the preparation of 3D printed objects containing liposomes and other nanoparticle-based nanomedicines,” concluded the authors.

[Source / Images: ‘Fabrication of 3D Printed Fish-Gelatin-Based Polymer Hydrogel Patches for Local Delivery of PEGylated Liposomal Doxorubicin’]

The post 3D Printed Medicine Uses Fish Gelatin to Deliver Cancer Treatment appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

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3DPOD: 3D Printing Podcast Episode 5: 3D Printing In Medicine

Hello everyone we really hope that you enjoy a new episode of the 3DPod. Maxwell Bogue and I had a lot of fun making this episode. In this 3DPod we talk about 3D printing in medicine. What impact is it making? What is happening in hospitals? What is happening in the developing world? We talk about implants, braces, personalized medicine, polymers and metals. We talk about DIY medicine and groups of people making their own medical devices and lots more. We really hope you enjoy this episode. As always do give us feedback and suggestions. You can find all of the podcasts including direct download, Spotify and Apple here.

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3D Printed Paracetamol Tablets Have Big Implications for Personalized Medicine

Drugs affect everyone differently. That’s why it’s so hard to find the right medication and right dosage to treat people with depression, for example, or why certain people don’t seem to get much relief from painkillers. That’s why the prospect of 3D printed medication is so exciting. Companies like FabRx are working to create medicines with personalized doses through 3D printing. Not only does 3D printing allow for different medications to be combined in one dose, but, as a new study shows, dosages can also be customized to suit people with different metabolic rates. The study, entitled “Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry,” was written by a group of researchers from the University of Nottingham and GlaxoSmithKline.

“Personalised medicine is defined as a customization of health care to individual patients through linking diagnostics and treatments with genetic testing and emerging technologies such as proteomics and metabolomics analysis,” the researchers state. “The main advantages of this approach are to increase the effectiveness of the prescribed treatment regimen and to minimise their adverse effects such as those linked to overdosing of drugs with a narrow therapeutic index such as digoxin and anti-clotting agents.”

Paracetamol, or acetaminophen, is one of the most commonly used over-the-counter painkillers, so the researchers selected it as the subject for their proof of concept study. Work has been done before using FDM 3D printing to formulate paracetamol tablets, they note, but the high extrusion temperature limits the potential active ingredients to only heat-stable ones. Other methods like SLA and ink-jet printing use excipients that are not generally recognized as safe, however, so FDM was chosen for the study.

A regenHU 3D bioprinter was used to print paracetamol into three different tablet geometries – solid, ring and mesh. The outer dimensions of the tablets were kept in the same oval shape, but the inner geometries were varied, as were the number of layers. The weights of the tablets were also kept consistent by varying their heights. The tablet surface area influenced the speed of the drug release – for example, with the mesh tablets, 70% of the drug was released within the first 15 minutes, while 25% was released from the ring tablets and 12% from the solid tablets in the same period of time.

Notably, each of the tablets contained the same dosage of paracetamol, but the different release rates meant that they would affect people in different ways. These release rates could, therefore, be tailored to specific patients’ metabolisms for the most effective treatment.

“The demonstrated ability to use a single unmodified formulation to achieve defined release profiles presents opportunities to optimise or personalise medicines during formulation development and in clinical use,” the researchers explain. “For example, relatively straightforward personalization of medicines would be possible for individuals with different metabolism rates due to their genetic makeup for certain drugs and hence could address issues where people who metabolise drugs slowly may accumulate a toxic level of a drug in the body or in others who process a drug quickly and never have high enough drug concentrations to be effective.”

Any drug is dangerous when taken in too-high doses, but some people tend to go overboard with painkillers such as paracetamol, because, as the researchers point out, they metabolize the drugs too quickly for them to be effective and thus think that more is better. More is toxic, in fact, but programming drugs so that their release rates are tailored to each individual’s metabolism means that the same dosage can be taken by different people and still have the proper effect on each one.

If this study could be applied to painkillers only, it would still be big news, but its potential goes beyond just paracetamol. Adverse effects could be minimized from drugs such as anticoagulants and antidepressants, even as they are tailored to be more effective to each individual patient. The prospect of personalized medicine through 3D printing has a lot of promise; one day we may look back on our current “one dosage fits all” standard as primitive medicine.

Authors of the paper include Shaban A. Khaled, Morgan R. Alexander, Derek J. Irvine, Ricky D. Wildman, Martin J. Wallace, Sonja Sharpe, Jae Yoo and Clive J. Roberts.

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