The design of manufacturing process of mold for producing polymeric dissolving microneedles

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Abstract

Introduction. Polymeric dissolving microneedles are promising way for drug delivery especially for vaccine delivery. It is an important task to create a scalable way of manufacture of dissolving polymeric microneedles. First step in this process is to create an easy and cheap way of producing negative master-molds for microneedles.

Objective. To develop the laser production technology of negative master-mold for dissolving polymeric microneedles.

Material and methods. Possibility of using different polymer plates (polydimethylsiloxane, polycarbonate, polystyrene, polypropylene, polymethyl methacrylate and polyethylene terephthalate) for producing negative microneedle molds and material’s surface free energy were examined. The modes of laser ablation of polymer and ways of its control were investigated. Pullulan dissolving microneedles were produced by using designed molds and examined by optical microscopy.

Results. Polyethylene terephthalate was chosen as the optimal polymer for producing negative microneedle mold because it leads to producing symmetrical microneedles with desired geometry. Also, the 2-step laser technology for the fabrication of polymeric microneedle molds and methods of mold’s quality control during manufacture was designed in this study. The technological scheme of polyethylene terephthalate microneedle mold’s manufacture was proposed in results of this study. The variety of manufacturing defects of polyethylene terephthalate microneedle mold and its’ causes were summarized.

Conclusion. The designed laser technology of producing negative microneedle molds in combination with right mold’s material (polyethylene terephthalate) can guarantee robust producing of dissolving polymeric microneedles and gives a possibility to scale it up.

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About the authors

Maria Sergeevna Zolotareva

MIREA – Russian Technological University

Email: mariya.zolotareva2014@yandex.ru
ORCID iD: 0000-0002-1597-6992

Senior Lecturer at the Biotechnology and Industrial Pharmacy Department of the Institute of Fine Chemical Technologies named after M.V. Lomonosov

Russian Federation, Moscow

Vladimir Stepanovich Kondratenko

MIREA – Russian Technological University

Email: kondratenko@mirea.ru
ORCID iD: 0000-0002-8940-4620

Doctor of Technical Sciences, Professor of the Nanoelectronics Department of the Institute of Advanced Technologies and Industrial Programming

Russian Federation, Moscow

Alexey Valerievich Panov

MIREA – Russian Technological University

Email: panov@mirea.ru
ORCID iD: 0000-0002-1603-143X

PhD in Chemical Sciences, Associate Professor of the Biotechnology and Industrial Pharmacy Department of the Institute of Fine Chemical Technologies named after M.V. Lomonosov

Russian Federation, Moscow

Stanislav Anatolievich Kedik

MIREA – Russian Technological University; Institute of Pharmaceutical Technologies

Author for correspondence.
Email: doctorkedik@yandex.ru
ORCID iD: 0000-0003-2610-8493

Doctor of Technical Sciences, Professor, Head of the Biotechnology and Industrial Pharmacy Department of the Institute of Fine Chemical Technologies named after M.V. Lomonosov

Russian Federation, Moscow; Moscow

References

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  2. Tang, S., Zhu, W., Wang, B-Z. Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches. J. Viruses. 2020; 12 (11): 10. doi: 10.3390/v12111212
  3. Sully R.E., Moore C.J., Garelick H., Loizidou E., Podoleanu A.G., Gubala V. Nanomedicines and microneedles: a guide to their analysis and application. Analytical Methods. 2021; 13: 3326–47. doi: 10.1039/D1AY00954K
  4. Korkmaz E., Friedrich E.E., Ramadan M.H., Erdos G., Mathers A.R., Burak Ozdoganlar O., Washburn N.R., Falo L.D., Jr. Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays. Acta Biomater. 2015; 24: 96–105. doi: 10.1016/j.actbio.2015.05.036
  5. Lee I-C., Lin W-M., Shu J-C., Tsai S-W., Chen C-H., Tsai M-T. Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice. Journal of Biomedical Materials Research Part A. 2017; 105A: 84–93. doi: 10.1002/jbm.a.35869
  6. Chen H., Wu B., Zhang M., Yang P., Yang B., Qin W., Wang Q., Wen X., Chen M., Quan G., Pan X., Wu C. A novel scalable fabrication process for the production of dissolving microneedle arrays. Drug Delivery and Translational Research. 2019; 9 (1): 240–8. doi: 10.1007/s13346-018-00593-z.
  7. Lutton R.E., Larrañeta E., Kearney M.C., Boyd P., Woolfson A.D., Donnelly R.F. A novel scalable manufacturing process for the production of hydrogel-forming microneedle arrays. International J. of pharmaceutics. 2015; 494 (1): 417–29. doi: 10.1016/j.ijpharm.2015.08.049.
  8. Vora L.K., Courtenay A.J., Tekko I.A., Larrañeta E., Donnelly R.F. Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules. International J. of Biological Macromolecules. 2020; 146: 290–8. doi: 10.1016/j.ijbiomac.2019.12.184
  9. Золотарева М.С., Кедик С.А., Кобыш А.Н., Кондратенко В.С., Панов А.В., Шигапов А.Э. Лазерное формирование микрополостей для изготовления растворяющихся полимерных микроигл. Приборы. 2022; 4: 37–41. [Zolotareva M.S., Kedik S.A., Kobysh A.N., Kondratenko V.S., Panov A.V., Shygapov A.E. Laser producing of microcavities for manufacturing dissolving polymeric microneedles. Instruments. 2022; 4: 37–41 (In Russian)]

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. The visualization of mold appearance: sectional (а) and top (б) view, 3D-model (в)

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3. Fig. 2. The scheme of the mold’s manufacturing

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4. Fig. 3. а – scheme of sectional view of the PMMA mold’s micro cavity; sectional view of the micro cavity along (line B) (б) and across (line A) the anisotropy lines (в); examples of asymmetrical microneedles with base diameter 300 μm in one section (г) and 150 μm in another one (д), example of symmetrical microneedle with base diameter 100 μm (е)

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5. Fig. 4. Photo of the polyethylene terephthalate microneedle mold (a), photo of a sectional view of the mold’s micro cavity (б) and photo of a microneedle made in it (в); photo of an RG-plastic mold made by 3D-printing (г) and photo of a microneedle made in it (д)

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6. Fig. 5. The sectional views of the polyethylene terephthalate microneedle mold’s micro cavity before (a) and after (б) 2% NaOH solution treatment under 70°С during 10 min; microneedles made in a treated (в, г) and untreated mold (д)

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7. Table 3_Fig. 1

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8. Table 3_Fig. 2

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9. Table 3_Fig. 3

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10. Table 3_Fig. 4

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11. Table 3_Fig. 5

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12. Fig. 6. The scheme of the sectional view of a polyethylene terephthalate microneedle mold for control of the micro cavity’s depth and profile

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13. Fig. 7. Technological scheme of the polyethylene terephthalate microneedle mold’s manufacturing

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