2026-04-17T10:13:26Zhttps://recercat.cat/oai/request

oai:recercat.cat:2117/4117712026-01-16T09:54:39Zcom_2072_1033col_2072_452950

00925njm 22002777a 4500 dc Ferrero, Carmen author Urpí Garriga, Lourdes author Aguilar de Leiva, Angela author Linares, V author Mora Castaño, Gloria author Millán Jiménez, Mónica author Martínez de Ilarduya Sáez de Asteasu, Domingo Antxon author Caraballo Rodríguez, Isidoro author 2024-05 The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ¿-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol-1) and a relatively low melting point (~65 °C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole. This work was part of the project RTI2018-095041-BC31 and was supported by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. Peer Reviewed Postprint (published version) Àrees temàtiques de la UPC::Enginyeria química Polymers -- Biodegradation Polymers in medicine Aliphatic copolyester Ultrasound-assisted compression 3D-printing semi-solid extrusion Metronidazole Drug delivery systems Sustained-release Polímers -- Biodegradació Polímers en medicina Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester