Skip to main content
SpringerLink
Log in

Influence of Crosslinker on Pullulan Hydrogel for Iontophoresis Controlled Transdermal Aspirin Release

  • Original Paper
  • Published:
Journal of Polymers and the Environment Aims and scope Submit manuscript

Abstract

Nowadays, transdermal drug delivery system (TDDS) has been developed continuously because it solves the problem of drug level inconsistencies in the blood and prevents the drug from being destroyed in the digestive tract. However, the limitations of TDDS are the low release rate of the patch and difficult penetration of the drug to the skin. Therefore, this research aims to study drug release behavior of aspirin with and without applied electrical potential for controlled drug release from the pullulan hydrogel patch using sodium trimetaphosphate and citric acid at various concentrations as the crosslinker. The pullulan hydrogel patches prepared by the solvent casting method were studied the release behavior by using a modified franz diffusion cell with containing pH 5.5 and 7.4 buffer solution at 37 ◦C for 2 h. The amount of drug release was compared with various electrical potentials as 0, 0.5, 1, 3, and 5 V. The aspirin release behavior from pullulan hydrogel was a Non-Fickian mechanism meaning that the aspirin was released via concentration gradient combined with swelling behavior of drug matrix. The amount of drug release and releasing rate was decreased with increasing the crosslinking ratio because of the lower the swelling behavior of matrix. In addition, the applied electrical stimulation enhanced the amount of drug release and releasing rate. The maximum release of aspirin is approximately 25% within 9 min from the hydrogel patch using sodium trimetaphosphate as a crosslinker and a 5 V which is higher than that of 0 V as 16% within 12 min.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lanas A, McCarthy D, Voelker M, Brueckner A, Senn S, Baron JA (2011) Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds—gastrointestinal adverse effects: a meta-analysis of randomized clinical trials. Drugs R D 11:277–288

    Article  PubMed  Google Scholar 

  2. Ammar HO, Ghorab M, El-Nahhas SA, Kamel R (2006) Design of a transdermal delivery system for aspirin as an antithrombotic drug. Int J Pharm 327(1–2):81–88

    Article  CAS  PubMed  Google Scholar 

  3. Wen H, Jung H, Li X (2015) Drug delivery approaches in addressing clinical pharmacology-related issues: opportunities and challenges. AAPS J 17:1327–1340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zaid Alkilani A, McCrudden MT, Donnelly RF (2015) Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics 7(4):438–470

    Article  PubMed Central  Google Scholar 

  5. Akhtar N, Singh V, Yusuf M, Khan RA (2020) Non-invasive drug delivery technology: development and current status of transdermal drug delivery devices, techniques and biomedical applications. Biomed Tech 65(3):243–272

    Article  CAS  Google Scholar 

  6. Berillo D, Zharkinbekov Z, Kim Y, Raziyeva K, Temirkhanova K, Saparov A (2021) Stimuli-Responsive polymers for Transdermal, Transmucosal and Ocular Drug Delivery. Pharmaceutics 13(12):2050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rizwan M, Yahya R, Hassan A, Yar M, Azzahari AD, Selvanathan V, Abouloula C (2017) N. pH sensitive hydrogels in drug delivery: brief history, properties, swelling, and release mechanism, material selection and applications. Polymers 9(4):137

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ho TC, Chang CC, Chan HP, Chung TW, Shu C, W, Chuang K, P, Tyan YC, Hydrogels (2022) Properties and applications in biomedicine. Mol 27(9):2902

    Article  CAS  Google Scholar 

  9. Ciolacu DE (2018) Structure-property relationships in cellulose-based hydrogels. Cellulose-based Superabsorbent Hydrogels ; 65–95

  10. Nasution H, Harahap H, Dalimunthe NF, Ginting MHS, Jaafar M, Tan OO, Herfananda AL (2022) Hydrogel and effects of crosslinking agent on cellulose-based hydrogels: a review. Gels 8(9):568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yang Q, Peng J, Xiao H, Xu X, Qian Z (2022) Polysaccharide hydrogels: functionalization, construction and served as scaffold for tissue engineering. Carbohydr Polym 278:118952

    Article  CAS  PubMed  Google Scholar 

  12. Zhu T, Mao J, Cheng Y, Liu H, Lv L, Ge M, Lai Y (2019) Recent progress of polysaccharide-based hydrogel interfaces for wound healing and tissue engineering. Adv Mater Interfaces 6(17):1900761

    Article  Google Scholar 

  13. Chatterjee S, Mahmood S, Hilles AR, Thomas S, Roy S, Provaznik V, Romero EL, Ghosal K (2023) Cationic starch: a functionalized polysaccharide based polymer for advancement of drug delivery and health care system-A review. Int J Biol Macromol. ; 125757

  14. El-Sayed NS, Kamel S (2022) Polysaccharides-based Injectable hydrogels: Preparation, characteristics, and Biomedical Applications. Colloids Interfaces 6(4):78

    Article  CAS  Google Scholar 

  15. Rajakumari R, Saha P, Ghosal K, Tharayil A, Kalarikkal N, Thomas S (2022) Polysaccharide-based scaffolds for tissue engineering applications. Polysaccharide-based Biomaterials: delivery of therapeutics and Biomedical Applications. The Royal Society of Chemistry, pp 535–558

  16. Prajapati VD, Jani GK, Khanda SM (2013) Pullulan: an exopolysaccharide and its various applications. Carbohydr Polym 95(1):540–549

    Article  CAS  PubMed  Google Scholar 

  17. Singh RS, Saini GK, Kennedy JF (2021) Pullulan production in stirred tank reactor by a colour-variant strain of Aureobasidium pullulans FB-1. Carbohydr Polym Technol Appl 2:100086

    CAS  Google Scholar 

  18. Bercea M (2022) Bioinspired hydrogels as platforms for life-science applications: challenges and opportunities. Polymers 14(12):2365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fang YY, Wang LJ, Li D, Li BZ, Bhandari B, Chen XD, Mao Z (2008) H. Preparation of crosslinked starch microspheres and their drug loading and releasing properties. Carbohydr Polym 74(3):379–384

    Article  CAS  Google Scholar 

  20. Yang J, Webb AR, Ameer G (2004) A. Novel citric acid-based biodegradable elastomers for tissue engineering. Adv Mater 16(6):511–516

    Article  CAS  Google Scholar 

  21. Wang H, Liao Y, Wu A, Li B, Qian J, Ding F (2019) Effect of sodium trimetaphosphate on chitosan-methylcellulose composite films: physicochemical properties and food packaging application. Polymers 11(2):368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Keirudin AA, Zainuddin N, Yusof NA (2020) Crosslinked carboxymethyl sago starch/citric acid hydrogel for sorption of Pb2+, Cu2+, Ni2 + and Zn2 + from aqueous solution. Polymers 12(11):2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim M, Jung B, Park JH (2012) Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomater 33(2):668–678

    Article  CAS  Google Scholar 

  24. Pairatwachapun S, Paradee N, Sirivat A (2016) Controlled release of acetylsalicylic acid from polythiophene/carrageenan hydrogel via electrical stimulation. Carbohydr Polym 137:214–221

    Article  CAS  PubMed  Google Scholar 

  25. Niamlang S, Sirivat A (2009) Electrically controlled release of salicylic acid from poly (p-phenylene vinylene)/polyacrylamide hydrogels. Int J Pharm 371(1–2):126–133

    Article  CAS  PubMed  Google Scholar 

  26. Lack S, Dulong V, Le Cerf D, Picton L, Argillier JF, Muller G (2004) Hydrogels based on Pullulan crosslinked with sodium trimetaphosphate (STMP): rheological study. Polym Bull 52:429–436

    Article  CAS  Google Scholar 

  27. Ismail H, Irani M, Ahmad Z (2013) Starch-based hydrogels: present status and applications. Int J Polym Mater Polym 62(7):411–420

    Article  CAS  Google Scholar 

  28. Krathumkhet N, Imae T, Paradee N (2021) Electrically controlled transdermal ibuprofen delivery consisting of pectin-bacterial cellulose/polypyrrole hydrogel composites. Cellulose 28:11451–11463

    Article  CAS  Google Scholar 

  29. Paradee N, Thanokiang J, Sirivat A (2021) Conductive poly (2-ethylaniline) dextran-based hydrogels for electrically controlled diclofenac release. Mater Sci Eng C 118:111346

    Article  CAS  Google Scholar 

  30. Jalal NR, Madrakian T, Afkhami A, Ghoorchian A (2021) Graphene oxide nanoribbons/polypyrrole nanocomposite film: controlled release of leucovorin by electrical stimulation. Electrochim Acta 370:137806

    Article  CAS  Google Scholar 

  31. Ruangmak K, Paradee N, Niamlang S, Sakunpongpitiporn P, Sirivat A (2022) Electrically controlled transdermal delivery of naproxen and indomethacin from porous cis-1, 4‐polyisoprene matrix. J Biomed Mater Res - B Appl 110(2):478–488

    Article  CAS  Google Scholar 

  32. Dulong V, Forbice R, Condamine E, Le Cerf D, Picton L (2011) Pullulan–STMP hydrogels: a way to correlate crosslinking mechanism, structure and physicochemical properties. Polym Bull 67:455–466

    Article  CAS  Google Scholar 

  33. Saeaeh K, Thummarungsan N, Paradee N, Choeichom P, Phasuksom K, Lerdwijitjarud W, Sirivat A (2019) Soft and highly responsive multi-walled carbon nanotube/pullulan hydrogel composites as electroactive materials. Eur Polym J 120:109231

    Article  Google Scholar 

  34. Mirzaee H, Khodaiyan F, Kennedy JF, Hosseini SS (2020) Production, optimization and characterization of pullulan from sesame seed oil cake as a new substrate by Aureobasidium pullulans. Carbohydr Polym Technol Appl 1:100004

    Google Scholar 

  35. Souto-Maior JFA, Reis AV, Pedreiro LN, Cavalcanti OA (2009) Phosphated crosslinked pectin as a potential excipient for specific drug delivery: preparation and physicochemical characterization. 2009 Soc Chem Ind 59:127–135

    Google Scholar 

  36. Banach M, Kowalski Z, Wzorek Z, Gorazda K (2009) A. chemical method of the production of heavy sodium tripolyphosphate with the high content of form I or Form II. Pol J Chem Technol 11(2):13–20

    Article  Google Scholar 

  37. Mali K, K, Dhawale SC, Dias RJ, Dhane NS, Ghorpade V (2018) S. citric acid crosslinked carboxymethyl cellulose-based composite hydrogel films for drug delivery. Indian J Pharm Sci 80(4):657–667

    Article  CAS  Google Scholar 

  38. Silva NT, Nascimento NF, Cividanes LS, Bertran CA, Thim G (2008) P. Kinetics of cordierite crystallization from diphasic gels. J Sol-Gel Sci Technol 47:140–147

    Article  CAS  Google Scholar 

  39. Mebrie A, Amare M, Kassa A, Yohannes YB, Tesfaye A, Abebe A, Asmelash T (2022) Novel poly (diaquabis (1, 10-phenanthroline) copper (II) chloride) modified glassy carbon electrode for square wave voltammetric determination of aspirin in tablet samples. Sens Int 3:100187

    Article  Google Scholar 

Download references

Acknowledgements

This research project is supported by Thailand Science Research and Innovation (TSRI), Basic Research Fund: Fiscal year 2021 under project number FRB640008 and KMUTT Research Center of Excellence Project.

Author information

Authors and Affiliations

  1. Sustainable Polymer & Innovative Composite Materials Research Group, Department of Chemistry, Faculty of Science, King Mongkut’s University of Technology Thonburi, Bangkok, 10140, Thailand

    Warinya Kongmee, Sitanan Poompoung, Nattinee Krathumkhet & Nophawan Paradee

  2. Conductive and Electroactive Polymers Research Unit, The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok, 10330, Thailand

    Anuvat Sirivat & Nophawan Paradee

Authors
  1. Warinya Kongmee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sitanan Poompoung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nattinee Krathumkhet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anuvat Sirivat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nophawan Paradee
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.K. and S.P.: Investigation, Writing – original draft. N.K.: Writing – review & editing. A.S.: review & editing. N.P.: Writing – review & editing, Supervision.

Corresponding author

Correspondence to Nophawan Paradee.

Ethics declarations

Competing Interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kongmee, W., Poompoung, S., Krathumkhet, N. et al. Influence of Crosslinker on Pullulan Hydrogel for Iontophoresis Controlled Transdermal Aspirin Release. J Polym Environ (2024). https://doi.org/10.1007/s10924-024-03239-z

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10924-024-03239-z

Keywords

Search

Navigation