AAPS PharmSciTech

, Volume 18, Issue 7, pp 2579–2585 | Cite as

Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin

  • Francisca Mano
  • Marta Martins
  • Isabel Sá-Nogueira
  • Susana Barreiros
  • João Paulo Borges
  • Rui L. Reis
  • Ana Rita C. Duarte
  • Alexandre Paiva
Research Article

Abstract

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.

KEY WORDS

anti-bacterial studies fast-dissolving drug delivery systems gelatin mandelic acid therapeutic deep-eutectic solvents 

Notes

ACKNOWLEDGEMENTS

The research leading to these results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the projects ENIGMA - PTDC/EQU-EPR/121491/2010 and UID/CTM/50025/2013, LAQV-REQUIMTE: UID/QUI/50006/2013, UCIBIO-REQUIMTE: UID/Multi/04378/2013 (co-financed by the ERDF under the PT2020 Partnership Agreement [POCI-01-0145-FEDER-007728]) and by FEDER through the COMPETE 2020 Programme. Marta Martins is grateful for financial support from FCT through the grant BIM/PTDC/EQUEPR/121491/2010/ENIGMA. This research has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS and from the project “Novel smart and biomimetic materials for innovative regenerative medicine approaches” RL1 - ABMR - NORTE-01-0124-FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).

REFERENCES

  1. 1.
    Robinson DH, Mauger JW. Drug delivery systems. Am J Hosp Pharm. 1991;48:S14–23.PubMedGoogle Scholar
  2. 2.
    Tiwari G, Tiwari R, Bannerjee S, Bhati L, Pandey S, Pandey P, et al. Drug delivery systems: an updated review. Int J Pharm Investig. 2012;2:2.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally disintegrating films: a modern expansion in drug delivery system. Saudi Pharm J. 2016;24:537–46.CrossRefPubMedGoogle Scholar
  4. 4.
    Lopez FL, Ernest TB, Tuleu C, Gul MO. Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms. Expert Opin Drug Deliv. 2015;12:1727–40.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Parkash V, Maan S, Deepika, Yadav S, Hemlata, Jogpal V. Fast disintegrating tablets: opportunity in drug delivery system. J Adv Pharm Technol Res. 2011;2:223.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ulery BD, Nair LS, Laurencin CT. Biomedical applications of biodegradable polymers. J Polym Sci B Polym Phys. 2011;49:832–64.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pilehvar-Soltanahmadi Y, Akbarzadeh A, Moazzez-Lalaklo N, Zarghami N. An update on clinical applications of electrospun nanofibers for skin bioengineering. Artif Cells Nanomed Biotechnol. 2015;1–15.Google Scholar
  8. 8.
    Lee KY, Jeong L, Kang YO, Lee SJ, Park WH. Electrospinning of polysaccharides for regenerative medicine. Adv Drug Deliv Rev Elsevier BV. 2009;61:1020–32.CrossRefGoogle Scholar
  9. 9.
    Kadajji VG, Betageri GV. Water soluble polymers for pharmaceutical applications. Polymers (Basel). 2011;3:1972–2009.CrossRefGoogle Scholar
  10. 10.
    Duarte ARC, Mano JF, Reis RL. Preparation of starch-based scaffolds for tissue engineering by supercritical immersion precipitation. J Supercrit Fluids. 2009;49:279–85.CrossRefGoogle Scholar
  11. 11.
    Jukola H, Nikkola L, Gomes ME, Reis RL, Ashammakhi N, Paulino GH, et al. Electrospun starch-polycaprolactone nanofiber-based constructs for tissue engineering. AIP Conf Proc. 2008;973:971–4.CrossRefGoogle Scholar
  12. 12.
    Ramakrishna S, Mayer J, Wintermantel E, Leong KW. Biomedical applications of polymer-composite materials: a review. Compos Sci Technol. 2001;61:1189–224.CrossRefGoogle Scholar
  13. 13.
    Sharifi F, Sooriyarachchi AC, Altural H, Montazami R, Rylander MN, Hashemi N. Fiber-based approaches as medicine delivery systems. ACS Biomater Sci Eng. 2016Google Scholar
  14. 14.
    Sajkiewicz P, Kołbuk D. Electrospinning of gelatin for tissue engineering—molecular conformation as one of the overlooked problems. J Biomater Sci Polym Ed. 2014;25:2009–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Williams DB, Carter CB. Transmission electron microscopy: a textbook for materials science, volume 3, 2nd ed. Springer; 2009.Google Scholar
  16. 16.
    Paiva A, Craveiro R, Aroso I, Martins M, Reis RL, Duarte ARC, et al. Natural deep eutectic solvents—solvents for the 21st century. Sustain Chem Eng. 2014;ASAP.Google Scholar
  17. 17.
    Zhang Q, De Oliveira VK, Royer S, Jérôme F. Deep eutectic solvents: syntheses, properties and applications. Chem Soc Rev. 2012;41:7108–46.CrossRefPubMedGoogle Scholar
  18. 18.
    Dai Y, van Spronsen J, Witkamp G-J, Verpoorte R, Choi YH. Natural deep eutectic solvents as new potential media for green technology. Anal Chim Acta Elsevier BV. 2013;766:61–8.CrossRefGoogle Scholar
  19. 19.
    Stott PW, Williams AC, Barry BW. Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. J Control Release. 1998;50:297–308.CrossRefPubMedGoogle Scholar
  20. 20.
    Aroso IM, Craveiro R, Rocha Â, Dionísio M, Barreiros S, Reis RL, et al. Design of controlled release systems for THEDES—therapeutic deep eutectic solvents, using supercritical fluid technology. Int J Pharm. 2015;492:73–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Aroso IM, Silva JC, Mano F, Ferreira ASD, Dionísio M, Sá-Nogueira I, et al. Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems. Eur J Pharm Biopharm. 2016;98:57–66.CrossRefPubMedGoogle Scholar
  22. 22.
    Yang C, Yu D-G, Pan D, Liu X-K, Wang X, Bligh SWA, et al. Electrospun pH-sensitive core–shell polymer nanocomposites fabricated using a tri-axial process. Acta Biomater. 2016;35:77–86.CrossRefPubMedGoogle Scholar
  23. 23.
    Wen H-F, Yang C, Yu D-G, Li X-Y, Zhang D-F. Electrospun zein nanoribbons for treatment of lead-contained wastewater. Chem Eng J. 2016;290:263–72.CrossRefGoogle Scholar
  24. 24.
    Yu D-G, Yang C, Jin M, Williams GR, Zou H, Wang X, et al. Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret. Colloids Surf B Biointerfaces. 2016;138:110–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Li D, Xia Y. Electrospinning of nanofibers: reinventing the wheel? Adv Mater. 2004;16:1151–70.CrossRefGoogle Scholar
  26. 26.
    Li Z, Wang C. Effects of working parameters on electrospinning. In: Springer, editor. One-dimensional nanostructures electrospinning Tech. Unique Nanofibers. Berlin, Heidelberg; 2013. p. 15–29.Google Scholar
  27. 27.
    Andrews JM. Determination of minimum inhibitory concentrations. J Antimicrob Chemother. 2001;48:5–16.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhang S, Huang Y, Yang X, Mei F, Ma Q, Chen G, et al. Gelatin nanofibrous membrane fabricated by electrospinning of aqueous gelatin solution for guided tissue regeneration. J Biomed Mater Res A. 2009;90:671–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Dos Santos R, Rocha Â, Matias A, Duarte C, Sá-Nogueira I, Lourenço N, et al. Development of antimicrobial Ion Jelly fibers. RSC Adv. 2013;3:24400.CrossRefGoogle Scholar
  30. 30.
    Pimenta A, Baptista A, Carvalho T, Brogueira P, Lourenço N, Afonso C, et al. Electrospinning of Ion Jelly fibers. Mater Lett Elsevier BV. 2012;83:161–4.CrossRefGoogle Scholar
  31. 31.
    Canejo JP, Borges JP, Godinho MH, Brogueira P, Teixeira PIC, Terentjev EM. Helical twisting of electrospun liquid crystalline cellulose micro- and nanofibers. Adv Mater. 2008;20:4821–5.CrossRefGoogle Scholar
  32. 32.
    Godinho MH, Canejo JP, Pinto LF V., Borges JP, Teixeira PIC. How to mimic the shapes of plant tendrils on the nano and microscale: spirals and helices of electrospun liquid crystalline cellulose derivatives. Soft Matter. 2009. p. 2772.Google Scholar
  33. 33.
    Koombhongse S, Liu W, Reneker DH. Flat polymer ribbons and other shapes by electrospinning. J Polym Sci Part B Polym Phys. 2001;39:2598–606.CrossRefGoogle Scholar
  34. 34.
    Doyle BB, Bendit EG, Blout ER. Infrared spectroscopy of collagen and collagen-like polypeptides. Biopolymers. 1975;14:937–57.CrossRefPubMedGoogle Scholar
  35. 35.
    Silverstein RM, Webster FX, Kiemle DJ. Spectrometric identification of organic compounds. Spectrom Identif Org Compd. 2006.Google Scholar
  36. 36.
    Riss TL, Moravec RA, Niles AL, Benink HA, Worzella TJ, Minor L. Cell viability assays. Assay Guid Man. 2004.Google Scholar
  37. 37.
    Jeon J-M, Lee H-I, Kim SG, Han S-H, So J-S. Differential inactivation of food poisoning bacteria and Lactobacillus sp. by mandelic acid. Food Sci Biotechnol. 2010;19:583–7.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • Francisca Mano
    • 1
  • Marta Martins
    • 2
    • 3
  • Isabel Sá-Nogueira
    • 4
  • Susana Barreiros
    • 1
  • João Paulo Borges
    • 5
  • Rui L. Reis
    • 2
    • 3
  • Ana Rita C. Duarte
    • 2
    • 3
  • Alexandre Paiva
    • 1
  1. 1.LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e TecnologiaUniversidade Nova de LisboaCaparicaPortugal
  2. 2.3B’s Research Group- Biomaterials, Biodegradable and BiomimeticUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineBarcoPortugal
  3. 3.ICVS/3B’s PT Government Associated LaboratoryBragaPortugal
  4. 4.UCIBIO-REQUIMTE, Departamento de Ciências da Vida, Faculdade de Ciências e TecnologiaUniversidade Nova de LisboaCaparicaPortugal
  5. 5.CENIMAT/I3N, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, FCTUniversidade Nova de LisboaLisbonPortugal

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