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.

Recent Advances of Taxol-Loaded Biocompatible Nanocarriers Embedded in Natural Polymer-Based Hydrogels

“…The rheological properties of GelMA hydrogels prepared using 5, 10 and 15% w/v of the polymer were not affected by the inclusion of Abraxane ® when 1.07 and 2.65 µg of nanoformulation per µl of hydrogel were used. On the contrary, the GelMA concentration influenced both the encapsulation efficiency as well as the in vitro release profiles of Abraxane ® [183]. Namely, 10% w/v of GelMA was shown to be a good compromise between entrapment yield and release sustainability.…”

“…Recently, Vigata and coworkers developed an implantable delivery system made up of gelatin functionalized with methacrylic anhydride (GelMA) for the controlled release of Abraxane ® [183]. The aim here was to obtain a suitable formulation to be used following surgical mastectomy or lumpectomy in order to prevent breast cancer recurrence [183].…”

“…Recently, Vigata and coworkers developed an implantable delivery system made up of gelatin functionalized with methacrylic anhydride (GelMA) for the controlled release of Abraxane ® [183]. The aim here was to obtain a suitable formulation to be used following surgical mastectomy or lumpectomy in order to prevent breast cancer recurrence [183]. The rheological properties of GelMA hydrogels prepared using 5, 10 and 15% w/v of the polymer were not affected by the inclusion of Abraxane ® when 1.07 and 2.65 µg of nanoformulation per µl of hydrogel were used.…”

Biomedical application of photo-crosslinked gelatin hydrogels

“…By comparing the loading of different concentrations of BMP-2, they found that the dose of growth factor in this system did not have much effect on efficiency (BMP-2 loaded at concentrations of 25 μg/ml result in 27.0% loaded growth factor maintained in the hydrogels for at least seven weeks). Margaux et al [38] developed a novel paclitaxel-based Abraxane delivery system based on GelMA. This drug delivery system can achieve high encapsulation efficiency (96%) without affecting its mechanical properties and the rate of drug release can be adjusted by controlling the concentration of GelMA (lower GelMA concentration will lead to longer drug release time).…”

Antitumor Effects of Self-Assembling Peptide-Emodin in situ Hydrogels in vitro and in vivo

“…20,21 Based on different tumor types and stages, a variety of hydrogel drug delivery systems have been developed. [22][23][24][25][26][27] Hydrogels are in an injectable solution, suspension or semi-solid state before administration and semi-solid or solid hydrogels can immediately form in situ at the site of drug administration through phase transition stimulated by external conditions (light, temperature, pH, etc.). [28][29][30][31] After the direct injection of the drug-loaded colloidal suspensions or solutions at the tumor site, the hydrogels can form in situ, and the drug loaded in the hydrogels can be mainly concentrated in the tumor tissue with improved therapeutic effects on tumors and reduced toxic effects of drugs on normal organs.…”