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Thermoresponsive poly(N-isopropylacrylamide) copolymer networks for galantamine hydrobromide delivery

Colloid and Polymer Science volume 298, pages 377–384 (2020)Cite this article

Abstract

Natural alkaloid galantamine is widely used for the treatment of Alzheimer’s disease and various other memory impairments. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solution. However, oral delivery of GH can cause side effects, such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery is one possible way to avoid such unwanted effects and is also patient friendly, especially for unconscious patients, patients with swallowing difficulties, and patients with mental disturbances. In this work, thermoresponsive copolymer networks based on poly(N-isopropylacrylamide) were studied as new platforms for potential transdermal GH delivery. Series of networks of varied structure and composition were synthesized and investigated by applying swelling kinetics and different spectroscopic and thermal methods. The network films were drug loaded in GH aqueous solution and main characteristics of the obtained GH delivery systems were evaluated. The GH release kinetic profiles in BS at 37 °C were established and discussed.

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References

  1. Giau VV, An SS, Bagyinszky E, Kim SY (2015) Next generation sequencing (NGS) gene panels and primers for studies on neurodegenerative disorders. Toxicol Environ Heal Sci 7:S32

    Google Scholar 

  2. Lyseng-Williamson KA, Plosker GL (2003) Spotlight on galantamine in Alzheimer’s disease. Disease Manag Health Outcome 11(2):125–128

    Article  Google Scholar 

  3. Robinson DM, Plosker GL (2006) Galantamine extended release. CNS Drugs 20(8):673–681

    CAS  Article  Google Scholar 

  4. Maltz MS, Kirschenbaum HL (2002) Galantamine: a new acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease. P&T 27(3):135–138

    Google Scholar 

  5. Drug label: REMINYL® (Galantamine HBr), (2001) tablets and oral solution, Food and Drug Administration

  6. Aleksiev A, Kostova B, Rachev D (2016) Development and optimization of the reservoir-type oral multiparticulate drug delivery systems of galantamine hydrobromide. Indian J Pharm Sci 78(3):368–376

    CAS  Article  Google Scholar 

  7. Biswal B, Sharma D (2013) Design, development and evaluation of galantamine hydrobromide bilayer sustained release tablet. Pharm Lett 5(6):12–19

    Google Scholar 

  8. Aleksiev A, Kostova B, Rachev D (2014) Development of Eudragit based sustained release systems of galantamine hydrobromide. Int J Pharm Sci Rev Res 27(1):135–140

    CAS  Google Scholar 

  9. Inglis F (2002) The tolerability and safety of cholinesterase inhibitors in the treatment of dementia. Int J Clin Pract Suppl 127:45–63

    CAS  Google Scholar 

  10. Small G, Dubois B (2007) A review of compliance to treatment in Alzheimer’s disease: potential benefits of a transdermal patch. Curr Med Res Opin 23(11):2705–2713

    CAS  Article  Google Scholar 

  11. Misra S, Chopra K, Sinha VR, Medhi B (2016) Galantamine-loaded solid–lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations. Drug Deliv 23(4):1434–1443

    CAS  Article  Google Scholar 

  12. Fornaguera C, Feiner-Gracia N, Caldero G, Garcia-Celma MJ, Solans C (2015) Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases. Nanoscale 7:12076–12084

    CAS  Article  Google Scholar 

  13. Hanafy AS, Farid RM, El Gamal SS (2015) Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer’s disease management: preparation and detection in rat brain. Drug Dev Ind Pharm 41:2055–2068

    CAS  Article  Google Scholar 

  14. Utsuki T, Uchimura N, Irikura M, Moriuchi H, Holloway HW, Yu QS, Spangler EL, Mamczarz J, Ingram DK, Irie T, Greig NH (2007) Preclinical investigation of the topical administration of phenserine: transdermal flux, cholinesterase inhibition, and cognitive efficacy. J Pharmacol Exp Ther 321(1):353–361

    CAS  Article  Google Scholar 

  15. Woo FY, Mahiran B, Mansor A, Maznah I (2015) Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system. Sci World J 2015:495271

    Google Scholar 

  16. Koetting MC, Peters JT, Steichen SD, Peppas NA (2015) Stimulus-responsive hydrogels: theory, modern advances, and applications. Mater Sci Eng R 93:1–49

    Article  Google Scholar 

  17. Hoffman AS (2013) Stimuli-responsive polymers: biomedical applications and challenges for clinical translation. Adv Drug Deliv Rev 65(1):10–16

    CAS  Article  Google Scholar 

  18. Yang J, Shen D, Zhou L, Li W, Li X, Yao C, Wang R, El-Toni AM, Zhang F, Zhao D (2013) Spatially confined fabrication of core-shell gold nanocages@mesoporous silica for near-infrared controlled photothermal drug release. Chem Mater 25:3030–3037

    CAS  Article  Google Scholar 

  19. Cui H, Liu Y, Cheng Y, Zhang Z, Zhang P, Chen X, Wei Y (2014) In vitro study of electroactive tetra aniline containing thermosensitive hydrogels for cardiac tissue engineering. Biomacromolecules 15:1115–1123

    CAS  Article  Google Scholar 

  20. Li L, Yan B, Yang J, Chen L, Zeng H (2015) Novel mussel-inspired injectable self-healing hydrogel with anti-biofouling property. Adv Mater 27:1294–1299

    CAS  Article  Google Scholar 

  21. Hoare TR, Kohane DS (2008) Hydrogels in drug delivery: progress and challenges. Polymer 49:1993–2007

    CAS  Article  Google Scholar 

  22. Calo E, Khutoryanskiy V (2015) Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polym J 65:252–267

    CAS  Article  Google Scholar 

  23. Li J, Mooney DJ (2016) Designing hydrogels for controlled drug delivery. Nat Rev Mater 1(12):1607–1611

    Article  Google Scholar 

  24. Zhuang J, Gordon MR, Ventura J, Li L, Thayumanavan S (2013) Multi-stimuli responsive macromolecules and their assemblies. Chem Soc Rev 42:7421–7435

    CAS  Article  Google Scholar 

  25. Lima LH, Morales Y, Cabral T (2016) Ocular biocompatibility of poly-N-isopropylacrylamide (pNIPAM). J Ophthalmol 2016:5356371

    Article  Google Scholar 

  26. Ohya S, Nakayama Y, Matsuda T (2004) In vivo evaluation of poly(N-isopropylacrylamide) (PNIPAM)-grafted gelatin as an in situ-formable scaffold. J Artif Organs 7:181–186

    CAS  Article  Google Scholar 

  27. Cho JH, Kim SH, Park KD, Jung MC, Yang WI, Han SW, Noh JY, Lee JW (2004) Chondrogenic differentiation of human mesenchymal stem cells using a thermosensitive poly(N-isopropylacrylamide) and water-soluble chitosan copolymer. Biomaterials 2:5743–5751

    Article  Google Scholar 

  28. Cao Y, Zhang C, Shen W, Cheng Z, Yu L, Ping Q (2007) Poly(N-isopropylacrylamide)–chitosan as thermosensitive in situ gel-forming system for ocular drug delivery. J Control Release 120:186–194

    CAS  Article  Google Scholar 

  29. Li W, Deng L, Moosa B, Wang G, Mashat A, Khashab NM (2014) “Nail” and “comb” effects of cholesterol modified NIPAm oligomers on cancer targeting liposomes. Biomater Sci 4:476–483

    Article  Google Scholar 

  30. Zhu X, Yan C, Winnik FM, Leckband D (2007) End-grafted low-molecular-weight PNIPAM does not collapse above the LCST. Langmuir 23:162–169

    CAS  Article  Google Scholar 

  31. Hoshino Y, Nakamoto M, Miura YJ (2012) Control of protein binding kinetics on synthetic polymer nanoparticles by tuning flexibility and inducing conformation changes of polymer chains. J Am Chem Soc 134:15209–15212

    CAS  Article  Google Scholar 

  32. Lanzalaco S, Armelin E (2017) Poly(N-isopropylacrylamide) and copolymers: a review on recent progresses in biomedical applications. Gels 3:36

    Article  Google Scholar 

  33. Satarkar NS, Hilt JZ (2008) Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. J Control Release 130:246–251

    CAS  Article  Google Scholar 

  34. Purushotham S, Chang PEJ, Rumpel H, Kee IHC, Ng RTH, Chow PKH, Tan CK, Ramanujan RV (2009) Thermoresponsive core-shell magnetic nanoparticles for combined modalities of cancer therapy. Nanotechnology 20(30):305101

    CAS  Article  Google Scholar 

  35. Qiu Y, Park K (2012) Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 64:49–60

    Article  Google Scholar 

  36. Huang G, Gao J, Hu Z, John JVS, Ponder BC, Moro D (2004) Controlled drug release from hydrogel nanoparticle networks. J Control Release 94:303–311

    CAS  Article  Google Scholar 

  37. Zhang XZh WDQ, Chu CC (2004) Synthesis, characterization and controlled drug release of thermosensitive IPN–PNIPAAm hydrogels. Biomaterials 25:3793–3805

    Article  Google Scholar 

  38. Georgieva D, Kostova B, Ivanova S, Rachev D, Tzankova V, Kondeva-Burdina M, Christova D (2014) pH-sensitive cationic copolymers of different macromolecular architecture as potential dexamethasone sodium phosphate delivery systems. J Pharm Sci 103:2406–2413

    CAS  Article  Google Scholar 

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Acknowledgments

The authors acknowledge Dr. Philip Ublekov for the XRD measurements and helpful discussion.

Funding

Part of this work is supported by the Bulgarian Ministry of Education and Science under the National Research Programme BioActiveMed: “Innovative Low-Toxic Bioactive Systems for Precision Medicine” (Grant D01-217/30.11.2018).

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Authors and Affiliations

  1. Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str, 1000, Sofia, Bulgaria

    Dilyana Georgieva, Bistra Kostova & Dimitar Rachev

  2. Institute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Str., Bl. 103-A, 1113, Sofia, Bulgaria

    Krasimira Ivanova-Mileva, Sijka Ivanova & Darinka Christova

Authors
  1. Dilyana Georgieva
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  2. Krasimira Ivanova-Mileva
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  3. Sijka Ivanova
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  4. Bistra Kostova
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  5. Dimitar Rachev
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  6. Darinka Christova
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Correspondence to Darinka Christova.

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Georgieva, D., Ivanova-Mileva, K., Ivanova, S. et al. Thermoresponsive poly(N-isopropylacrylamide) copolymer networks for galantamine hydrobromide delivery. Colloid Polym Sci 298, 377–384 (2020). https://doi.org/10.1007/s00396-020-04621-8

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  • DOI: https://doi.org/10.1007/s00396-020-04621-8

Keywords

  • Polymer networks
  • Thermoresponsive polymers
  • Galantamine hydrobromide
  • Drug release