Ex vivo permeation testing of 3d-printed microneedles for depression using human skin
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0000-0002-8740-1661 Date
2024-09-18
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Jagiellonian University Medical College
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Abstract
INTRODUCTION Emerging technologies such as 3D printing are intensively investigated regarding therapy personalization. The flexibility of that technology enables the manufacturing of dosage forms and drug delivery systems in different sizes and shapes. 3D printing is one of the methods for obtaining microneedle systems. Microneedles are tiny needles, usually placed on a joint base. Thanks to the sharp tip and optimal geometry, they can pierce the skin and deliver the drug without causing discomfort. Moreover, physically crossing the stratum corneum barrier can improve drug delivery efficiency. Agomelatine is an antidepressant with very low bioavailability after oral administration due to the first-pass effect. Delivering agomelatine transdermally using a microneedle system could potentially improve its bioavailability and reduce doses during the therapy. The study aimed to compare different 3D-printed microneedle systems containing agomelatine regarding drug permeation ability through the human skin ex vivo. The systems differed in size, shape, and drug loading method, which could impact the permeation rate and profile. MATERIALS AND METHODS Microneedle systems were obtained using a 3D printing method based on curing the photosensitive resin with UV light. Two methods of drug loading were applied: either coating with a gel containing the drug or incorporation of the substance into the system at the stage of manufacturing. Two types of geometries (pyramids and cones) were used. Permeation studies Permeation studies were performed using Franz diffusion cells (Teledyne Hanson Research, USA) and full-thickness human skin. The skin was obtained from patients who had undergone surgical operations (Biopredic International, France). Samples of the skin with microneedles were placed on Franz diffusion cells. Phosphate Buffered Saline (PBS) pH=7,4 was used as the acceptor media. Due to the prolonged experiment time (7 days), sodium azide (0,02% w/v) was added to the PBS as an antimicrobial agent. During the study, samples of acceptor fluid were taken at specified time points and immediately replaced with a fresh medium. The samples were analysed using HPLC (Shimadzu, Nexera, Japan). Determining the amount of drug in tissue After the experiment, pieces of the skin were cut and placed in the homogenizing tubes. The mixture of water and ethanol was added to the tubes. Samples were homogenized and centrifuged. The supernatant was filtered and drug amount was analyzed. RESULTS AND DISCUSSION The full-thickness human skin used in the experiment mimicked the natural skin barrier. It allowed for the assessment of whether the systems were sharp enough to be inserted into the skin during application. Obtained microneedle systems were suitable for piercing the skin. Agomelatine released from the microneedles penetrated through the skin to the acceptor fluid, which can potentially simulate transdermal delivery. However, some of the drug was held in the skin tissue. All formulations were investigated for seven days to obtain a complete view of the permeation profile. Depending on the drug loading method, the release profile differed. The microneedle systems with drug incorporated at the manufacturing stage tended to show linear correlation between cumulative drug amount in the acceptor fluid and time. However, in the case of a coated system, the release showed a two-stage profile characterized by faster release at the beginning and linear correlation at the second stage. Microneedle systems obtained by the same 3D printing technique and loaded using the same method showed various release rates, probably due to the difference in microneedle geometry. CONCLUSIONS The study on Franz diffusion cells using full-thickness human skin ex vivo allowed for comparing the permeation abilities of various 3D-printed microneedle systems. Microneedles delivered the drug through the skin into the acceptor fluid. Depending on the drug loading method, the systems differed in their permeation profile. Still, in both cases, it was a slow process lasting over seven days, which indicates the potential for sustained drug delivery. The geometry of the microneedle system did not affect the permeation profile but impacted the system’s loading capacity. Funding source: The work was performed as a result of the research project no. 2021/42/E/NZ7/00125 (ID: 526262) financed by the National Science Centre (Poland).
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This repository contains the conference material related to the oral presentation entitled “Ex vivo permeation testing of 3D-printed microneedles for depression using human skin”, presented during the 3rd International Conference on Contemporary Pharmacy Challenges: “Enhancing pharmaceuticals through interdisciplinary research”, held on 16–18 September 2024 in Kraków, Poland. The conference was organized by Jagiellonian University Medical College.
The material describe studies on 3D-printed microneedle systems containing agomelatine, designed for potential transdermal delivery in the treatment of depression. The presented work focused on ex vivo permeation testing using human skin, with comparison of systems differing in microneedle geometry, 3D-printing method, and drug-loading strategy.
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Wojtyłko M, Lamprou DA, Froelich A, Jadach B, Kuczko W, Wichniarek R, Szybowicz M, Nowicka A, Kordyl O, Krysztofiak J, Białek A, Osmałek T. Ex vivo permeation testing of 3D-printed microneedles for depression using human skin. In: Book of Abstracts: 3rd International Conference on Contemporary Pharmacy Challenges — ICCPC 2024: “Enhancing pharmaceuticals through interdisciplinary research”; 16–18 September 2024; Kraków, Poland. Jagiellonian University Medical College; 2024.