In Vitro Tests of FDM 3D-Printed Diclofenac Sodium-Containing Implants.

Petra Arany,Ildikó Papp,Ferenc Fenyvesi,István Budai,Mónika Béres,János Elek,Vecsernyés Miklós,Marianna Zichar,Judit Váradi,Gábor Vasvári,Géza Regdon,Ádám Haimhoffer,Máté Csontos,Pálma Fehér,Ildikó Bácskay,Rudolf Gesztelyi,Zoltán Ujhelyi

doi:10.3390/molecules25245889

Petra Arany, Ildikó Papp + Show 15 more

Open Access

https://doi.org/10.3390/molecules25245889

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Abstract

One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravimetric and heatflow assay, contact angle measurement, scanning electron microscopy, microcomputed tomography, and Raman spectroscopy. Based on our results, it can be stated that the samples are considered nontoxic. The dissolution profiles are influenced by the material properties of the polymers, the diameter, and the infill percentage. Our results confirm the potential of fused deposition modeling (FDM) 3D printing for the manufacturing of different implantable drug delivery systems in personalized medicine and may be applied during surgical interventions.

Highlights

Personalized medicine may be used to provide patient-specific treatment during surgeries.Surgical implants and local drug delivery can be united, and their synergy incorporates surgical and medical treatment into a one-step medication that offers unique therapeutic advantages: the ability to raise the effectiveness, decrease the amount of the used active pharmaceutical ingredients (APIs), minimize adverse effects, and increase patient compliance [1,2]
In the case of polylactic acid (PLA) and antibacterial PLA, the printing temperature was 215 ◦ C; polyethylene terephthalate glycol (PETG) was printed at 250 ◦ C, and poly(methyl methacrylate) (PMMA) was printed at 270 ◦ C
Throughout the preparation, neither the high printing temperature (215–270 ◦ C) nor the ventilation had an impact on the API stability, as confirmed by TG/DSC investigations

Summary

Introduction

Personalized medicine may be used to provide patient-specific treatment during surgeries.Surgical implants and local drug delivery can be united, and their synergy incorporates surgical and medical treatment into a one-step medication that offers unique therapeutic advantages: the ability to raise the effectiveness, decrease the amount of the used active pharmaceutical ingredients (APIs), minimize adverse effects, and increase patient compliance [1,2]. Personalized medicine may be used to provide patient-specific treatment during surgeries. Based on an experiment, customized implants in orthopedic surgeries can reduce the treatment time and improve the medical outcomes [4]. The APIs used have to be stable during printing, which means they must have high heat tolerance, stability in different solvents, compatibility with cross-linking polymers, and tolerance to UV light. It is a fast prototyping technique, it is not able to exceed the productivity of an industrial-sized tableting machine [7]

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