Skip to main content

Advertisement

SpringerLink
Log in

Fabrication of Carboxymethylcellulose-Gelatin Dissolving Microneedle Patch for Pain-Free, Efficient, and Controlled Transdermal Delivery of Insulin

  • Original Article
  • Published:
Journal of Pharmaceutical Innovation Aims and scope Submit manuscript

Abstract

Purpose

Dissolving microneedle patches are attracting attention as they are associated with improved patient compliance and safety.

Methods

This study fabricated dissolving microneedle (DMN) patches from modified sodium carboxymethylcellulose (CMC) and gelatin might be as an alternative to subcutaneous injection for the transdermal delivery of insulin.

Results

The prepared DMNs exhibited excellent mechanical strength to penetrate the skin and confocal microscopy showed gradual diffuse from the puncture sites to deeper tissue up to more than 750–800 µm. The in vitro study was performed by a dissolution apparatus and ex vivo by the Franz diffusion cell system mainly quantified by human insulin ELISA kit where the release study exhibited excellent results with constant and stable delivery up to 96 ± 2%. The in vivo study results confirmed an ideal drug release profile up to 95 ± 2% until 8 h in 24-h study and thus insulin-loaded CMC-gelatin formulation is suitable for drug encapsulation, having excellent dissolving factor and penetration depth and avoiding drug loss. A home applicator played an important role in improving the efficacy and stability and faster insulin release rate. The plasma insulin level and blood glucose level (BGL) were calculated and were maintained and a stable decrease in 3–4 h was observed compared to SC injection route with the same insulin dose.

Conclusion

These results suggest that the CMC-gelatin DMN patch loaded with insulin has great potential in diabetes treatment for both type 1 and 2 diabetic patients in a relatively painless, rapid, and convenient manner.

Graphical Abstract

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Availability of Data and Material

Access to data will be granted from the authors on reasonable request.

References

  1. Lee JW, Park JH, Prausnitz MR. Dissolving microneedles for transdermal drug delivery. Biomaterials. 2008;29(13):2113–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen MC, et al. Chitosan microneedle patches for sustained transdermal delivery of macromolecules. Biomacromol. 2012;13:4022–31.

    Article  CAS  Google Scholar 

  3. Donnelly RF. Microneedle-mediated intradermal delivery. Chichester: Wiley; 2012. p. 113–46.

    Book  Google Scholar 

  4. Baishali J, Ashish W. Microneedle. Future prospect for efficient drug delivery in future diabetes management - a review. Indian J Pharmacol. 2019;51(1):1–7.

    Google Scholar 

  5. Giudice EL, Campbell JD. Needle-free vaccine delivery. Adv Drug Deliv Rev. 2006;58(1):68–89.

    Article  CAS  PubMed  Google Scholar 

  6. Li L, et al. Preparation of glucose responsive and fluorescent micelles via a combination of RAFT polymerization and chemoenzymatic transesterification for controlled release of insulin. RSC Adv. 2015;5:75766–72.

    Article  CAS  Google Scholar 

  7. Liu D, et al. Oral delivery of insulin using CaCO3-based composite nanocarriers with hyaluronic acid coatings. Mater Lett. 2016;188:263–6.

    Article  Google Scholar 

  8. Ito Y, et al. Two-layered dissolving microneedles formulated with intermediate-acting insulin. Int J Pharm. 2012;436(1–2):387–93.

    Article  CAS  PubMed  Google Scholar 

  9. Ito Y, et al. Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats. Drug Dev Ind Pharm. 2011;37(12):1387–93.

    Article  CAS  PubMed  Google Scholar 

  10. Ito Y, et al. Transdermal insulin application system with dissolving microneedles. Diabetes Technol Ther. 2012;14(10):891–9.

    Article  CAS  PubMed  Google Scholar 

  11. Liu S, et al. Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin. Eur J Pharm Biopharm. 2014;86:267–76.

    Article  CAS  PubMed  Google Scholar 

  12. Weijiang Y, et al. Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin. Mater Sci Eng C Mater Bio Appl. 2017;80:187–96.

    Article  Google Scholar 

  13. Kim M, Jung B, Park JH. Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials. 2012;33:668–78.

    Article  CAS  PubMed  Google Scholar 

  14. Liu S, et al. The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J Control Release. 2012;161:933–41.

    Article  CAS  PubMed  Google Scholar 

  15. Naito S, et al. Antigen- loaded dissolving microneedle array as a novel tool for percutaneous vaccination. Vaccine. 2012;30:1191–7.

    Article  CAS  PubMed  Google Scholar 

  16. Chih HC, Victor BH, Chien TC. Dissolving microneedle patches for transdermal insulin delivery in diabetic mice: potential for clinical applications. Materials (Basel). 2018;11(9):1625.

    Article  Google Scholar 

  17. Ling MH, Chen MC. Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats. Acta Biomater. 2013;9:8952–61.

    Article  CAS  PubMed  Google Scholar 

  18. Yu W, et al. Transdermal delivery of insulin with bioceramic composite microneedles fabricated by gelatin and hydroxyapatite. Mater Sci Eng C. 2017;73:425–8.

    Article  CAS  Google Scholar 

  19. Yu W, et al. Fabrication of biodegradable composite microneedles based on calcium sulfate and gelatin for transdermal delivery of insulin. Mater Sci Eng C. 2017;71:725–34.

    Article  CAS  Google Scholar 

  20. Lee IC, et al. Formulation of two layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice. J Biomed Mater Res. 2017;105:84–93.

    Article  CAS  Google Scholar 

  21. Yujie Z, et al. A dissolving and glucose responsive insulin-releasing microneedle patch for type 1 diabetes therapy. J Mater Chem B. 2021;9:648–57.

    Article  Google Scholar 

  22. Na Z, et al. Dissolving polymer microneedles for transdermal delivery of insulin. Front Pharmacol. 2021;12: 719905.

    Article  Google Scholar 

Download references

Acknowledgements

The author gratefully acknowledges the fellowship received from Indian Council of Medical Research (ICMR), New Delhi (Ref No.: 45/38/2018/MP/BMS) for carrying out research in this field. We thank the team of APT Research Foundation, Pune, for helpful discussion and support for in vivo studies. We also acknowledge technical support provided by IRCC IIT Bombay and SAIF IIT Bombay.

Funding

Funding was received from Indian Council of Medical Research (ICMR)—New Delhi (Ref No.: 45/38/2018/MP/BMS) for carrying out this whole project.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Nilgiris, Ooty, Tamil Nadu, 643001, India

    Baishali A Jana & Ashish Wadhwani

  2. Nanomedicine Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, 400076, Maharashtra, India

    Riyaz Ali Osmani, Sanket Jaiswal & Rinti Banerjee

  3. Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India

    Veera Venkata Satyanarayana Reddy Karri

  4. Faculty of Health of Sciences, School of Pharmacy, JSS Academy of Higher Education and Research, Vacoas-Phoenix, 73304, Mauritius

    Ashish Wadhwani

Authors
  1. Baishali A Jana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Riyaz Ali Osmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanket Jaiswal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rinti Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Veera Venkata Satyanarayana Reddy Karri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ashish Wadhwani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Baishali A. Jana was involved in the conceptualization, methodology, experiments, software, data curation, writing—original draft preparation, investigation. Riyaz Ali Osmani was involved in the experiments, investigation, software, editing, data curation. Sanket Jaiswal was involved in experiments, software, data curation. Rinti Banerjee was involved in supervision, reviewing, validation, and visualization. Veera Venkata Satyanarayana Reddy Karri was involved in visualization, reviewing, and editing. Ashish Wadhwani was involved in the conceptualization, visualization, validation, reviewing, editing, and supervision.

Corresponding author

Correspondence to Ashish Wadhwani.

Ethics declarations

Ethics Approval

All the experiments were approved by the APT Research Foundation (National Toxicological Centre, NTC), Pune, in accordance with the guidelines for animal experimentation of NTC (RP 35_1920 approval number).

Consent to Participate

Not applicable.

Consent for Publication

All the authors consent to publication.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor 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

Jana, B.A., Osmani, R.A., Jaiswal, S. et al. Fabrication of Carboxymethylcellulose-Gelatin Dissolving Microneedle Patch for Pain-Free, Efficient, and Controlled Transdermal Delivery of Insulin. J Pharm Innov 18, 653–664 (2023). https://doi.org/10.1007/s12247-022-09670-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12247-022-09670-w

Keywords

Search

Navigation