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An Oral 3D Printed PLGA-Tocopherol PEG Succinate Nanocomposite Hydrogel for High-Dose Methotrexate Delivery in Maintenance Chemotherapy

ABSTRACT: High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop a novel drug delivery system employing TPGS and a biodegradable polymer, i.e., PLGA, to construct methotrexate-loaded nanoparticles fixated in alginate-gelatine 3D printable hydrogel ink to form a solid 3D printed tablet for oral delivery. The results indicated that high accuracy (>95%) of the 3D printed tablets was achieved using a 25 G needle. In vitro, drug release profiles were investigated at pH 1.2 and pH 7.4 to simulate the gastrointestinal environment. The in vitro release profile displayed a controlled and prolonged release of methotrexate over 24 h. The in silico modeling study displayed P-gp ATPase inhibition, suggesting enhanced MTX absorption from the gastrointestinal site. The 3D-printed hydrogel-based tablet has the potential to overcome the chemotherapeutic challenges that are experienced with conventional therapies.

SUBMITTER: Kondiah P

PROVIDER: S-EPMC9313284 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Earlier, various attempts to develop graphene structures using chemical and nonchemical routes were reported. Being efficient, scalable, and repeatable, 3D printing of graphene-based polymer inks and aerogels seems attractive; however, the produced structures highly rely on a binder or an ice support to stay intact. The presence of a binder or graphene oxide hinders the translation of the excellent graphene properties to the 3D structure. In this communication, we report our efforts to synthesize a 3D-shaped 3D graphene (3D2G) with good quality, desirable shape, and structure control by combining 3D printing with the atmospheric pressure chemical vapor deposition (CVD) process. Direct ink writing has been used in this work as a 3D-printing technique to print nickel powder-PLGA slurry into various shapes. The latter has been employed as a catalyst for graphene growth via CVD. Porous 3D2G with high purity was obtained after etching out the nickel substrate. The conducted micro CT and 2D Raman study of pristine 3D2G revealed important features of this new material. The interconnected porous nature of the obtained 3D2G combined with its good electrical conductivity (about 17 S/cm) and promising electrochemical properties invites applications for energy storage electrodes, where fast electron transfer and intimate contact with the active material and with the electrolyte are critically important. By changing the printing design, one can manipulate the electrical, electrochemical, and mechanical properties, including the structural porosity, without any requirement for additional doping or chemical postprocessing. The obtained binder-free 3D2G showed a very good thermal stability, tested by thermo-gravimetric analysis in air up to 500 °C. This work brings together two advanced manufacturing approaches, CVD and 3D printing, thus enabling the synthesis of high-quality, binder-free 3D2G structures with a tailored design that appeared to be suitable for multiple applications.

Dataset Information

An Oral 3D Printed PLGA-Tocopherol PEG Succinate Nanocomposite Hydrogel for High-Dose Methotrexate Delivery in Maintenance Chemotherapy

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