Inkjet Printing of Proteins: an Experimental Approach
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Peptides and proteins represent a promissory group of molecules used by the pharmaceutical industry for drug therapy with great potential for development. However, the administration of these molecules presents a series of difficulties, making necessary the exploration of new alternatives like the buccal route of administration to improve drug therapy compliance. Although drop-on demand printers have been explored for small molecule drugs with promising results, the development of delivery systems for peptides and proteins through inkjet printing has seen little development. Therefore, the aim of this study was to assess the feasibility of using a thermal inkjet printing system for dispensing lysozyme and ribonuclease-A as model proteins. To address the absorption limitations of a potential buccal use, a permeation enhancer (sodium deoxycholate) was also studied in formulations. We found that a conventional printer successfully printed both proteins, exhibiting very high printing efficiency. Furthermore, the protein structure was not affected and minor effects were observed in the enzymatic activity after the printing process. In conclusion, we provide evidence for the usage of an inexpensive, easy to use, reliable, and reproducible thermal inkjet printing system to dispense proteins solutions for potential buccal application. Our research significantly contributes to present an alternative for manufacturing biologics delivery systems, with emphasis in buccal applications. Next steps of developments will be aimed at the use of new materials for printing, controlled release, and protection strategies for proteins and peptides.
KEY WORDSbuccal films inkjet printing lysozyme peptides ribonuclease-A
M. Montenegro-Nicolini acknowledges the funding support from CONICYT 21150995. J.O. Morales thanks the financial support from FONDECYT 11130235 and FONDAP 15130011.
Compliance with Ethical Standards
Conflict of Interest
The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.
- 7.MonoSol Rx. MonoSol Rx and the PharmFilm pipeline [Internet]. 2015 [cited 2015 Nov 16]. Available from: http://www.monosolrx.com/content/pipeline/overview.htm.
- 9.Lindén M. Hot-melt extrusion of modified release pellets-influence of the formulation and extrusion process on extended-and enteric release profile. 2012 [cited 2015 Nov 1]; Available from: http://publications.lib.chalmers.se/records/fulltext/158879.pdf.
- 10.Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A review of hot-melt extrusion: process technology to pharmaceutical products. ISRN Pharm [Internet]. 2012 [cited 2015 Oct 21];2012. Available from: http://downloads.hindawi.com/journals/isrn.pharmaceutics/2012/436763.pdf.
- 27.Le HP. Progress and trends in ink-jet printing technology [Internet]. 1998 [cited 2015 Mar 28]. Available from: http://ist.publisher.ingentaconnect.com/content/ist/jist/1998/00000042/00000001/art00007.
- 31.Merck KGaA. Product information: Glycerol 85%. Darmstadt, Germany.Google Scholar
- 36.Daly R, Harrington TS, Martin GD, Hutchings IM. Inkjet printing for pharmaceutics—a review of research and manufacturing. Int J Pharm [Internet]. [cited 2015 Mar 28]; Available from: http://www.sciencedirect.com/science/article/pii/S0378517315002331.
- 41.Sigma-Aldrich. Product information: lysozyme from chicken egg white for molecular biology. St. Louis, USA.Google Scholar
- 42.Sigma-Aldrich. Product information: ribonuclease A from bovine pancreas for molecular biology. St. Louis, USA.Google Scholar
- 43.Rathbone M, Senel S, Pather I. Oral mucosal drug delivery and therapy. Springer; 2015. 289 p.Google Scholar
- 44.Fan X, Li J, Liu H, Xu N. Using porous polyethylene sheets in late surgical intervention for orbital blowout fractures. Zhonghua Yan Ke Za Zhi [Chin J Ophthalmol]. 2003;39(9):516–9.Google Scholar
- 48.Kisler JM, Stevens GW, O Connor AJ. Adsorption of proteins on mesoporous molecular sieves. Mater Phys Mech. 2001;4:89–93.Google Scholar
- 49.Ramm LE, Whitlow MB, Mayer MM. The relationship between channel size and the number of C9 molecules in the C5b-9 complex. J Immunol Baltim Md 1950. 1985;134(4):2594–9.Google Scholar
- 52.Gibson M. Pharmaceutical preformulation and formulation: a practical guide from candidate drug selection to commercial dosage form. CRC Press; 2016. 562 p.Google Scholar
- 55.Ikeda K, Hamaguchi K, Miwa S, Nishina T. Circular dichroism of human lysozyme. J Biochem (Tokyo). 1972;71(3):371–8.Google Scholar
- 60.CRC Handbook of Chemistry and Physics, 94th Edition [Internet]. CRC Press. 2013 [cited 2016 May 22]. Available from: https://www.crcpress.com/CRC-Handbook-of-Chemistry-and-Physics-94th-Edition/Haynes/p/book/9781466571143.