3D-printed reservoir-type implants containing poly(lactic acid)/poly(caprolactone) porous membranes for sustained drug delivery

Implantable drug delivery systems are an interesting alternative to conventional drug delivery systems to achieve local or systemic drug delivery. In this work, we investigated the potential of fused-deposition modelling to prepare reservoir-type implantable devices for sustained drug delivery. An antibiotic was chosen as a model molecule to evaluate the potential of this type of technology to prepare implants on-demand to provide prophylactic antimicrobial treatment after surgery. The first step was to prepare and characterize biodegradable rate-controlling porous membranes based on poly(lactic acid) (PLA) and poly(caprolactone) (PCL). These membranes were prepared using a solvent casting method. The resulting materials contained different PLA/PCL ratios. Cylindrical implants were 3D-printed vertically on top of the membranes. Tetracycline (TC) was loaded inside the implants and drug release was evaluated. The results suggested that membranes containing a PLA/PCL ratio of 50/50 provided drug release over periods of up to 25 days. On the other hand, membranes containing lower PCL content did not show a porous structure and accordingly the drug could not permeate to the same extent.

Highlights

• Poly(lactic acid) (PLA) and poly(caprolactone) (PCL) have been combined effectively to create porous membranes for drug delivery applications

• PLA/PCL membranes were successfully combined with fused deposition modelling to prepare implantable devices

• The implants prepared in this work provided sustained release of tetracycline for periods of at least 4 weeks

• 3D-printed implants loaded with tetracycline showed antimicrobial properties against E.coli and S. aureus for at least 21 days.

• The resulting implants showed excellent cytocompatibility when tested using human umbilical vein endothelial cells.

The influence of different parameters on drug release was evaluated. It was established that film thickness, drug content and implant size are critical parameters as they have a direct influence on drug release kinetics. In all cases the implants were capable of providing drug release for at least 25 days. The antimicrobial properties of the implants were evaluated against E. coli and S. aureus. The resulting implants showed antimicrobial properties at day 0 and even after 21 days against both type of microorganisms. Finally, the biocompatibility of the implants was evaluated using endothelial cells. Cells exposed to implants were compared with a control group. There were no differences between both groups in terms of cell proliferation and morphology.

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Anna Korelidou, Juan Domínguez-Robles, Elizabeth Magill, Magdalini Eleftheriadou, Victoria A. Cornelius, Ryan F. Donnelly, Andriana Margariti, Eneko Larrañeta,
3D-printed reservoir-type implants containing poly(lactic acid)/poly(caprolactone) porous membranes for sustained drug delivery,
Biomaterials Advances, 2022, 213024, ISSN 2772-9508,
https://doi.org/10.1016/j.bioadv.2022.213024.