4.8 Article

3D printed PLGA implants: How the filling density affects drug release

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 363, Issue -, Pages 1-11

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2023.09.020

Keywords

PLGA; Implant; 3D printing; Ibuprofen; Swelling; Drug release mechanism

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Different types of ibuprofen-loaded, poly (D,L lactic-co-glycolic acid) (PLGA)-based implants were prepared by 3D printing. The effect of filling density on drug release was investigated and it was found that filling density significantly influenced the release kinetics and the shape of the release curve. This can be explained by the presence (or absence) of a continuous aqueous phase between the polymeric filaments and the role of substantial system swelling in controlling drug release.
Different types of ibuprofen-loaded, poly (D,L lactic-co-glycolic acid) (PLGA)-based implants were prepared by 3D printing (Droplet Deposition Modeling). The theoretical filling density of the mesh-shaped implants was varied from 10 to 100%. Drug release was measured in agarose gels and in well agitated phosphate buffer pH 7.4. The key properties of the implants (and dynamic changes thereof upon exposure to the release media) were monitored using gravimetric measurements, optical microscopy, Differential Scanning Calorimetry, Gel Perme-ation Chromatography, and Scanning Electron Microscopy. Interestingly, drug release was similar for implants with 10 and 30% filling density, irrespective of the experimental set-up. In contrast, implants with 100% filling density showed slower release kinetics, and the shape of the release curve was altered in agarose gels. These observations could be explained by the existence (or absence) of a continuous aqueous phase between the polymeric filaments and the orchestrating role of substantial system swelling for the control of drug release. At lower filling densities, it is sufficient for the drug to be released from a single filament. In contrast, at high filling densities, the ensemble of filaments acts as a much larger (more or less homogeneous) polymeric matrix, and the average diffusion pathway to be overcome by the drug is much longer. Agarose gel (mimicking living tissue) hinders substantial PLGA swelling and delays the onset of the final rapid drug release phase. This improved mechanistic understanding of the control of drug release from PLGA-based 3D printed implants can help to facilitate the optimization of this type of advanced drug delivery systems.

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