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Laser engineered polymer thin films as drug delivery systems

Abstract

This study is focused on the fabrication of thin films of hydroxypropyl methylcellulose (HPMC) and ethyl cellulose (EC) polymer blends impregnated with captopril via matrix assisted pulsed laser evaporation (MAPLE) for the design of transdermal patches. The laser engineered polymer blend: captopril films are evaluated for physicochemical characteristics such as film morphology, chemistry of the films surface, drug content, and in vivo animal irritancy and skin sensitivity studies. The morphological investigation of the MAPLE fabricated coatings, i.e., by atomic force microscopy reveals that the morphology and topography of the polymer: drug films may be tuned by adjusting the HPMC: EC ratio in the MAPLE target. In addition, by tuning the HPMC: EC ratio in the as-deposited MAPLE films, it is possible to adjust the drug release profile. The Fourier-transform infrared spectroscopy investigation showed no interaction between captopril and the polymers (HPMC: EC) used. The skin irritation studies carried out on rabbits, showed no noticeable skin reactions, thus pointing out the compatibility of captopril with both the polymer blend and with the skin. In addition, no skin sensitization was noted among the guinea pigs that were challenged with the MAPLE fabricated transdermal patches. To sum up, the application of matrix-assisted pulsed laser evaporation for the fabrication of hydrophilic: hydrophobic polymer blends shows that there is great potential for the development of transdermal drug delivery system of captopril.

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Data availability

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

References

  1. M.N. Pastore, Y.N. Kalia, M. Horstmann, M.S. Roberts, Br J Pharmacol. 172(9), 2179–2209 (2015)

    Google Scholar 

  2. D. Bird, N.M. Ravindra, Med Devices Sens. 3, e10069 (2020)

    Google Scholar 

  3. Y.Q. Yu, X. Yang, X.F. Wu, Y.B. Fan, Front. Bioeng. Biotechnol. 9, 646554 (2021)

    Google Scholar 

  4. S. Korani, S. Bahrami, M. Korani, M. Banach, T.P. Johnston, A. Sahebkar, Lipids Health Dis. 18(1), 193 (2019)

    Google Scholar 

  5. I. Singh, A.P. Morris, Int J Pharm Investig. 1(1), 4–9 (2011)

    Google Scholar 

  6. T. Tanner, R. Marks, Skin Res. Technol. 14, 249–260 (2008)

    Google Scholar 

  7. T. Unger, C. Borghi, F. Charchar, N.A. Khan, N.R. Poulter, D. Prabhakaran, A. Ramirez, M. Schlaich, G.S. Stergiou, M. Tomaszewski, R.D. Wainford, B. Williams, A.E. Schutt, Hypertension 75, 1334–1357 (2020)

    Google Scholar 

  8. T.D. Giles, B.J. Materson, J.N. Cohn, J.B. Kostis, J. Clin. Hypertens. 11, 611–614 (2009)

    Google Scholar 

  9. D.R. Gullick, W.J. Pugh, M.J. Ingram, P.A. Cox, G.P. Moss, Drug Dev. Ind. Pharm. 36(8), 926–932 (2010)

    Google Scholar 

  10. D.A. Smith, K. Beaumont, T.S. Maurer, L. Di, J. Med. Chem. 61(10), 4273–4282 (2018)

    Google Scholar 

  11. A. Ahad, M. Aqil, K. Kohli, Y. Sultana, M. Mujeeb, A. Ali, Asian J. Pharm. Sci. 5, 276–288 (2010)

    Google Scholar 

  12. K.A. Walters, K.R. Brain, Dermatological formulation and transdermal systems, in Dermatological and transdermal formulations. ed. by K.A. Walters (Informa, New York, 2002), pp.319–400

    Google Scholar 

  13. S. Güngör, Y. Ozsoy, Ther. Deliv. 3(9), 1101–1116 (2012)

    Google Scholar 

  14. E. Verhoeven, C. Vervaet, J.P. Remon, Eur. J. Pharm. Biopharm. 63, 320–330 (2006)

    Google Scholar 

  15. R. Enayatifard, M. Saeedi, J. Akbari, Y. HaeriTabatabaee, Trop. J. Pharm Res. 8(5), 425 (2009)

    Google Scholar 

  16. M.J. Vasques, B. Perez-Marcus, J.L. Gomez-Amora, R. Martinez-Pacheo, C. Souto, A. Concheiro, Drug Dev. Ind. Pharm. 18, 1355–1375 (1992)

    Google Scholar 

  17. Y. Okuda, Y. Irisawa, K. Okimoto, T. Osawa, S. Yamashita, Int. J. Pharm. 423(2), 351–359 (2012)

    Google Scholar 

  18. X.-Y. Shi, T.-W. Tan, Biomaterials 23(23), 4469–4473 (2002)

    Google Scholar 

  19. A. Arunachalam, M. Karthikeyan, V.D. Kumar, M. Prathap, S. Sethuraman, S. Ashutoshkumar, S. Manidipa, Curr. Pharma Res. 1(1), 70–81 (2010)

    Google Scholar 

  20. G. Raj, R. Raveendran, Introduction to Basics of Pharmacology and Toxicology Volume 1: General and Molecular Pharmacology: Principles of Drug Action (Springer Nature Singapore Pte Ltd., Singapore, 2019)

    Google Scholar 

  21. P.K. Wu, J. Fitzgerald, A. Pique, D.B. Chrisey, R.A. McGill, Mater. Res. Soc. Symp. Proc. 617, J2.3.1-6 (2000)

    Google Scholar 

  22. J. Schou, Appl. Surf. Sci. 255, 5191 (2009)

    ADS  Google Scholar 

  23. C. Constantinescu, A. Palla-Papavlu, A. Rotaru, P. Florian, F. Chelu, M. Icriverzi, A. Nedelcea, V. Dinca, A. Roseanu, M. Dinescu, Appl. Surf. Sci. 255, 5491 (2009)

    ADS  Google Scholar 

  24. A.T. Sellinger, E.M. Leveugle, K. Gogick, L.V. Zhigilei, J.M. Fitz-Gerald, J. Vacuum Sci. Technol. A 24, 1618 (2006)

    ADS  Google Scholar 

  25. Y. Wang, H. Jeong, M. Chowdhury, C.B. Arnold, R.D. Priestley, Polym. Cryst. 1, e10021 (2018)

    Google Scholar 

  26. D.B. Chrisey, A. Piqué, R.A. McGill, J.S. Horwitz, B.R. Ringeisen, D.M. Bubb, P.K. Wu, Chem. Rev. 103(2), 553 (2003)

    Google Scholar 

  27. N.L. Dumitrescu, M. Icriverzi, A. Bonciu, P. Florian, A. Moldovan, A. Roseanu, L. Rusen, V. Dinca, F. Grama, Int. J. Mol. Sci. 23, 3988 (2022)

    Google Scholar 

  28. A. Palla-Papavlu, V. Dinca, M. Dinescu, F. Di Pietrantonio, D. Cannatà, M. Benetti, E. Verona, Appl. Phys. A 105, 651–659 (2011)

    ADS  Google Scholar 

  29. R. Cristescu, A. Doraiswamy, T. Patz, G. Socol, S. Grigorescu, E. Axente, F. Sima, R.J. Narayan, D. Mihaiescu, A. Moldovan, I. Stamatin, I.N. Mihailescu, B. Chisholm, D.B. Chrisey, Appl. Surf. Sci. 253, 7702 (2007)

    ADS  Google Scholar 

  30. I.A. Paun, V. Ion, A. Moldovan, M. Dinescu, Appl. Phys. Lett. 96, 243702 (2010)

    ADS  Google Scholar 

  31. A.P. Caricato, V. Arima, M. Catalano, M. Cesaria, P.D. Cozzoli, M. Martino, A. Taurino, R. Rella, R. Scarfiello, T. Tunno, A. Zacheo, Appl. Surf. Sci. 302, 92–98 (2014)

    ADS  Google Scholar 

  32. D.A. Cristian, F. Grama, R. Papagheorghe, S. Brajnicov, V. Ion, S. Vizireanu, A. Palla-Papavlu, M. Dinescu, Appl. Phys. A 125, 424 (2019)

    ADS  Google Scholar 

  33. H.G. Brittain, H. Kadin, Pharm. Res. 7, 1082–1085 (1990)

    Google Scholar 

  34. C.H. Lee, H.I. Maibach, Contact Dermatitis 33(1), 1–7 (1995)

    Google Scholar 

  35. B. Magnusson, A.M. Kligman, J. Investig. Dermatol. 52, 268–276 (1969)

    Google Scholar 

  36. A. Fahs, M. Brogly, S. Bistac, M. Schmitt, Carbohydr. Polym. 80(1), 105–114 (2010)

    Google Scholar 

  37. N.A. Camino, O.E. Pérez, C. Carrera Sanchez, J.M. Rodriguez Patino, A.M.R. Pilosof, Food Hydrocolloids 23(8), 2359–2368 (2009)

    Google Scholar 

  38. N.K. Anuar, W.T. Wui, D.K. Ghodgaonkar, M.N. Taib, J. Pharm. Biomed. Anal. 43(2), 549–557 (2007)

    Google Scholar 

  39. M.K. Trivedi, A. Branton, D. Trivedi, G. Nayak, R.K. Mishra, S. Jana, J. Biomed. Mater. Res. 3(6), 83–91 (2015)

    Google Scholar 

  40. S. Cavalu, S. CintaPinzaru, V. Chis, Rom. J. Biophys. 17(3), 195–203 (2007)

    Google Scholar 

  41. H. Jancovics, C. Pettinari, F. Marchetti, E. Kamu, L. Nagy, S. Troyanov, L. Pellerito, J. Inorg. Biochem. 97, 370–376 (2003)

    Google Scholar 

  42. A. Palla-Papavlu, L. Rusen, V. Dinca, M. Filipescu, T. Lippert, M. Dinescu, Appl. Surf. Sci. 302, 87–91 (2014)

    ADS  Google Scholar 

  43. P.E. Luner, E. Oh, Colloids Surf. A 181, 31 (2001)

    Google Scholar 

  44. L. Li, S. Roethel, V. Breedveld et al., Cellulose 20, 3219–3226 (2013)

    Google Scholar 

  45. P.C. Faria-Tischer, C.A. Tischer, L. Heux et al., Mater. Sci. Eng. C Mater. Biol. Appl. 51, 167–173 (2015)

    Google Scholar 

  46. T. Kiss, T. Alapi, G. Varga, C. Bartos, R. Ambrus, P. Szabo-Revesz, G. Katona, J. Pharm. Sci. 108(8), 2552–2560 (2019)

    Google Scholar 

  47. M. Ci, J. Liu, S. Shang, Z. Jiang, P. Zhu, S. Sui, Fibers Polym. 21, 2179–2185 (2020)

    Google Scholar 

  48. S. Belbekhouche, J. Bras, G. Siqueira, C. Chappey, L. Lebrun, B. Khelifi, S. Marais, A. Dufresne, Carbohydr. Polym. 83, 1740–1748 (2011)

    Google Scholar 

  49. S. Van Nguyen, B.K. Lee, Cellulose 28, 5693–5705 (2021)

    Google Scholar 

  50. M. Larsson, A. Johnsson, S. Gårdebjer, R. Bordes, A. Larsson, Mater. Des. 122, 414–421 (2017)

    Google Scholar 

  51. H. Bera, Y.F. Abbasi, V. Gajbhiye, K.F. Liew, P. Kumar, P. Tambe, A.K. Azad, D. Cun, M. Yang, Mater. Sci. Eng. C 110, 110628 (2020)

    Google Scholar 

  52. R.W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, N.A. Peppas, Int. J. Pharm. 15(1), 25–35 (1983)

    Google Scholar 

  53. A.K. Azad, S.M.A. Al-Mahmood, B. Chatterjee, W.M.A. Wan Sulaiman, T.M. Elsayed, A.A. Doolaanea, Pharmaceutics 12, 219 (2020)

  54. M.S. Latif, A.K. Azad, A. Nawaz, S.A. Rashid, M.H. Rahman, S.Y. Al Omar, S.G. Bungau, L. Aleya, M.M. Abdel-Daim, Polymers 13, 3455 (2021)

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Acknowledgements

Financial support from the Romanian Ministry of Research, Innovation and Digitalization under Romanian National Core Program LAPLAS VII—contract no. 30N/2023, and UEFISCDI, through projects PN-II-RU-TE-2011-3-0267 and PN-III-P4-ID-PCE-2020-2375 is gratefully acknowledged. The authors would like to thank Dr. Ionut Tirca for acquiring part of the polymer: drug thin films by MAPLE and Dr. Valentina Mărăscu for acquiring the FTIR spectra.

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Bonciu, A., Cremer, L., Calugaru, A. et al. Laser engineered polymer thin films as drug delivery systems. Appl. Phys. A 129, 327 (2023). https://doi.org/10.1007/s00339-023-06608-y

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