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Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel.

ABSTRACT: Hydrogels are excellent candidates for the sustained local delivery of anticancer drugs, as they possess tunable physicochemical characteristics that enable to control drug release kinetics and potentially tackle the problem of systemic side effects in traditional chemotherapeutic delivery. Yet, current systems often involve complicated manufacturing or covalent bonding processes that are not compatible with regulatory or market reality. Here, we developed a novel gelatin methacryloyl (GelMA)-based drug delivery system (GelMA-DDS) for the sustained local delivery of paclitaxel-based Abraxane®, for the prevention of local breast cancer recurrence following mastectomy. GelMA-DDS readily encapsulated Abraxane® with a maximum of 96% encapsulation efficiency. The mechanical properties of the hydrogel system were not affected by drug loading. Tuning of the physical properties, by varying GelMA concentration, allowed tailoring of GelMA-DDS mesh size, where decreasing the GelMA concentration provided overall more sustained cumulative release (significant differences between 5%, 10%, and 15%) with a maximum of 75% over three months of release, identified to be released by diffusion. Additionally, enzymatic degradation, which more readily mimics the in vivo situation, followed a near zero-order rate, with a total release of the cargo at various rates (2-14 h) depending on GelMA concentration. Finally, the results demonstrated that Abraxane® delivery from the hydrogel system led to a dose-dependent reduction of viability, metabolic activity, and live-cell density of triple-negative breast cancer cells in vitro. The GelMA-DDS provides a novel and simple approach for the sustained local administration of anti-cancer drugs for breast cancer recurrence.

SUBMITTER: Vigata M

PROVIDER: S-EPMC7077643 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel.

Vigata Margaux M Meinert Christoph C Pahoff Stephen S Bock Nathalie N Hutmacher Dietmar W DW

Polymers 20200224 2

Hydrogels are excellent candidates for the sustained local delivery of anticancer drugs, as they possess tunable physicochemical characteristics that enable to control drug release kinetics and potentially tackle the problem of systemic side effects in traditional chemotherapeutic delivery. Yet, current systems often involve complicated manufacturing or covalent bonding processes that are not compatible with regulatory or market reality. Here, we developed a novel gelatin methacryloyl (GelMA)-ba ...[more]

PMID: 32102478

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Project description:The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100?µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17?±?0.50 um/s and took less than 8?minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99?±?0.40 ?m/s) than larger molecules such as dextran (2.26?±?0.55 ?m/s with 4?kDa) or BSA (0.33?±?0.07 ?m/s with 66.5?kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2?hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

Dataset Information

Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel.

Publications

Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel.

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