Skip to main content

Advertisement

SpringerLink
Log in

Preparation and characterization of dissolving hyaluronic acid composite microneedles loaded micelles for delivery of curcumin

  • Short Communication
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

In order to improve the bioavailability of curcumin (Cur) and patient compliance, a type of novel hyaluronic acid (HA) composite microneedles containing Cur-loaded micelles was designed in this paper. On the one hand, the microneedles matrix solution was prepared by screening the optimal concentration of HA and the better proportion of HA to sodium carboxymethyl starch (CMS-Na). On the other hand, the amphiphilic polymer, named as Quercetin-Dithiodipropionic Acid-Oligomeric Hyaluronic Acid (Que-DA-oHA), was synthesized and characterized using 1H-NMR. Subsequently, the dialysis method was used to prepare Cur-loaded Que-DA-oHA micelles with an average size of 172.6 ± 11.4 nm and zeta potential of − 33.71 ± 0.45 mV. A micromolding process was used to prepare the micelle-loaded HA composite microneedles. It had been found that when the concentration of HA was 200 mg/mL and the mass ratio of HA to CMS-Na was 2:1, the prepared HA composite microneedles had good mechanical strength. In-skin dissolution kinetics showed that the micelle-loaded HA composite microneedles could dissolve quickly in the skin. In vitro permeation study indicated that the microneedles delivered 74.7% of their drug load over 6 h, which exhibited remarkable drug permeation properties in a short time. Here, we creatively combined micellar technology with microneedle technology to rapidly deliver Cur transdermally for diseases treatment such as melanoma.

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
Fig. 10
Fig. 11

References

  1. Ngo HV, Tran PHL, Lee BJ, Tran TTD. Development of film-forming gel containing nanoparticles for transdermal drug delivery. Nanotechnology. 2019;30(41):415102.

    Article  CAS  PubMed  Google Scholar 

  2. Larese Filon F, Mauro M, Adami G, Bovenzi M, Crosera M. Nanoparticles skin absorption: new aspects for a safety profile evaluation. Regul Toxicol Pharmacol. 2015;72(2):310–22.

    Article  CAS  PubMed  Google Scholar 

  3. Larrañeta E, Lutton REM, Woolfson AD, Donnelly RF. Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development. Mater Sci Eng R Rep. 2016;104:1–32.

    Article  Google Scholar 

  4. Khan S, Minhas MU, Tekko IA, Donnelly RF, Thakur RRS. Evaluation of microneedles-assisted in situ depot forming poloxamer gels for sustained transdermal drug delivery. Drug Deliv Transl Res. 2019;9(4):764–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sharma S, Hatware K, Bhadane P, Sindhikar S, Mishra DK. Recent advances in microneedle composites for biomedical applications: advanced drug delivery technologies. Mater Sci Eng C Mater Biol Appl. 2019;103:109717.

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Lin SQ, Quan GL, Hou AL, Yang PP, Peng TT, Gu YK, et al. Strategy for hypertrophic scar therapy: improved delivery of triamcinolone acetonide using mechanically robust tip-concentrated dissolving microneedle array. J Control Release. 2019;306:69–82.

    Article  CAS  PubMed  Google Scholar 

  8. Choi JT, Park SJ, Park JH. Microneedles containing cross-linked hyaluronic acid particulates for control of degradation and swelling behaviour after administration into skin. J Drug Target. 2018;26(10):884–94.

    Article  CAS  PubMed  Google Scholar 

  9. Eliezer M, Imber JC, Sculean A, Pandis N, Teich S. Hyaluronic acid as adjunctive to non-surgical and surgical periodontal therapy: a systematic review and meta-analysis. Clin Oral Investig. 2019;23(9):3423–35.

    Article  PubMed  Google Scholar 

  10. Barclay TG, Day CM, Petrovsky N, Garg S. Review of polysaccharide particle-based functional drug delivery. Carbohydr Polym. 2019;221:94–112.

    Article  CAS  PubMed  Google Scholar 

  11. Chen DQ, Lian SN, Sun JF, Liu ZL, Zhao F, Jiang YT, et al. Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition. Drug Deliv. 2016;23(3):808–13.

    Article  PubMed  Google Scholar 

  12. Wang KL, Guo CJ, Dong X, Yu YM, Wang BJ, Liu WH, et al. In vivo evaluation of reduction-responsive alendronate-hyaluronan-curcumin polymer-drug conjugates for targeted therapy of bone metastatic breast cancer. Mol Pharm. 2018;15(7):2764–9.

    Article  CAS  PubMed  Google Scholar 

  13. Guo LF, Shi MB, Song N, Wan ZR, Liu H, Liu LH. Anchorage of curcumin onto PVP enhances anti-tumor effect of curcumin. Med Chem Res. 2019;28(5):646–56.

    Article  CAS  Google Scholar 

  14. Sun MD, Zhang Y, He Y, Xiong MH, Huang HY, Pei SC, et al. Green synthesis of carrier-free curcumin nanodrugs for light-activated breast cancer photodynamic therapy. Colloids Surf B: Biointerfaces. 2019;180:313–8.

    Article  CAS  PubMed  Google Scholar 

  15. Zhao SJ, Pi C, Ye Y, Zhao L, Wei YM. Recent advances of analogues of curcumin for treatment of cancer. Eur J Med Chem. 2019;180:524–35.

    Article  CAS  PubMed  Google Scholar 

  16. Peng SF, Li ZL, Zou LQ, Liu W, Liu CM, McClements DJ. Enhancement of curcumin bioavailability by encapsulation in sophorolipid-coated nanoparticles: an in vitro and in vivo study. J Agric Food Chem. 2018;66(6):1488–97.

    Article  CAS  PubMed  Google Scholar 

  17. Chen DQ, Yu HY, Sun KX, Liu WH, Wang HB. Dual thermoresponsive and pH-responsive self-assembled micellar nanogel for anticancer drug delivery. Drug Deliv. 2014;21(4):258–64.

    Article  CAS  PubMed  Google Scholar 

  18. Neisy A, Zal F, Seghatoleslam A, Alaee S. Amelioration by quercetin of insulin resistance and uterine GLUT4 and ERalpha gene expression in rats with polycystic ovary syndrome (PCOS). Reprod Fertil Dev. 2019;31(2):315–23.

    Article  CAS  PubMed  Google Scholar 

  19. Tiwari S, Shishodia SK, Shankar J. Docking analysis of hexanoic acid and quercetin with seven domains of polyketide synthase A provided insight into quercetin-mediated aflatoxin biosynthesis inhibition in Aspergillus flavus. 3 Biotech. 2019;9(4):149.

    Article  PubMed  PubMed Central  Google Scholar 

  20. de Granada-Flor A, Sousa C, Filipe HAL, Santos M, de Almeida RFM. Quercetin dual interaction at the membrane level. Chem Commun (Camb). 2019;55(12):1750–3.

    Article  Google Scholar 

  21. Nagula RL, Wairkar S. Recent advances in topical delivery of flavonoids: a review. J Control Release. 2019;296:190–201.

    Article  CAS  PubMed  Google Scholar 

  22. Ramoller IK, Tekko IA, McCarthy HO, Donnelly RF. Rapidly dissolving bilayer microneedle arrays - a minimally invasive transdermal drug delivery system for vitamin B12. Int J Pharm. 2019;566:299–306.

    Article  CAS  PubMed  Google Scholar 

  23. Wang BJ, Zhang W, Zhou XD, Liu MN, Hou XY, Cheng ZT, et al. Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer. Drug Deliv. 2019;26(1):1265–79.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zheng YH, You XR, Guan SY, Huang J, Wang LY, Zhang JY, et al. Poly(ferulic acid) with an anticancer effect as a drug nanocarrier for enhanced colon cancer therapy. Adv Funct Mater. 2019;29(15):1808646.

    Article  Google Scholar 

  25. Liu MN, Wang BJ, Guo CJ, Hou XY, Cheng ZT, Chen DQ. Novel multifunctional triple folic acid, biotin and CD44 targeting pH-sensitive nano-actiniaes for breast cancer combinational therapy. Drug Deliv. 2019;26(1):1002–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ripolin A, Quinn J, Larraneta E, Vicente-Perez EM, Barry J, Donnelly RF. Successful application of large microneedle patches by human volunteers. Int J Pharm. 2017;521(1–2):92–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Quinn HL, Hughes CM, Donnelly RF. In vivo and qualitative studies investigating the translational potential of microneedles for use in the older population. Drug Deliv Transl Res. 2018;8(2):307–16.

    Article  CAS  PubMed  Google Scholar 

  28. Kang G, Kim S, Yang H, Jang M, Chiang L, Baek JH, et al. Combinatorial application of dissolving microneedle patch and cream for improvement of skin wrinkles, dermal density, elasticity, and hydration. J Cosmet Dermatol. 2019;18(4):1083–91.

    Article  PubMed  Google Scholar 

  29. Chiu YH, Chen MC, Wan SW. Sodium hyaluronate/chitosan composite microneedles as a single-dose intradermal immunization system. Biomacromolecules. 2018;19(6):2278–85.

    Article  CAS  PubMed  Google Scholar 

  30. Yang J, Liu XL, Fu YZ, Song YJ. Recent advances of microneedles for biomedical applications: drug delivery and beyond. Acta Pharm Sin B. 2019;9(3):469–83.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Szunerits S, Boukherroub R. Heat: a highly efficient skin enhancer for transdermal drug delivery. Front Bioeng Biotechnol. 2018;6:15.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chen BZ, Ashfaq M, Zhang XP, Zhang JN, Guo XD. In vitro and in vivo assessment of polymer microneedles for controlled transdermal drug delivery. J Drug Target. 2018;26(8):720–9.

    Article  CAS  PubMed  Google Scholar 

  33. Chen JM, Huang WY, Huang ZY, Liu SQ, Ye YL, Li QL, et al. Fabrication of tip-dissolving microneedles for transdermal drug delivery of meloxicam. AAPS PharmSciTech. 2018;19(3):1141–51.

    Article  CAS  PubMed  Google Scholar 

  34. Yu JC, Zhang YQ, Ye YQ, DiSanto R, Sun WJ, Ranson D, et al. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc Natl Acad Sci U S A. 2015;112(27):8260–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shi CL, Guo X, Qu QQ, Tang ZM, Wang Y, Zhou SB. Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles. Biomaterials. 2014;35(30):8711–22.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang YJ, Guo ZY, Cao ZL, Zhou WX, Zhang Y, Chen QJ, et al. Endogenous albumin-mediated delivery of redox-responsive paclitaxel-loaded micelles for targeted cancer therapy. Biomaterials. 2018;183:243–57.

    Article  CAS  PubMed  Google Scholar 

  37. Su YJ, Liu Y, Xu XT, Zhou JP, Xu L, Xu XL, et al. On-demand versatile prodrug nanomicelle for tumor-specific bioimaging and photothermal-chemo synergistic cancer therapy. ACS Appl Mater Interfaces. 2018;10(45):38700–14.

    Article  CAS  PubMed  Google Scholar 

  38. Feng CL, Han YX, Guo HH, Ma XL, Wang ZQ, Wang LL, et al. Self-assembling HA/PEI/dsRNA-p21 ternary complexes for CD44 mediated small active RNA delivery to colorectal cancer. Drug Deliv. 2017;24(1):1537–48.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge and thank Dr. Yanping Zhu for providing access and analysis to 1H-NMR for our studies.

Funding

This study was financially supported by Taishan Scholar Program to Daquan Chen (No. qnts20161035); Shandong Provincial Natural Science Foundation (No. ZR2019ZD24, ZR2019YQ30), Open fund project of Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine(TCM-0906).

Author information

Author notes

  1. Ziting Cheng and Hua Lin contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People’s Republic of China

    Ziting Cheng, Zhen Wang, Xiaoyu Yang, Mei Zhang, Xuechun Liu, Bingjie Wang & Daquan Chen

  2. Medical Center, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People’s Republic of China

    Hua Lin

  3. Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China

    Zhenfeng Wu

Authors
  1. Ziting Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hua Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoyu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xuechun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bingjie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhenfeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daquan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhenfeng Wu or Daquan Chen.

Ethics declarations

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, Z., Lin, H., Wang, Z. et al. Preparation and characterization of dissolving hyaluronic acid composite microneedles loaded micelles for delivery of curcumin. Drug Deliv. and Transl. Res. 10, 1520–1530 (2020). https://doi.org/10.1007/s13346-020-00735-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-020-00735-2

Keywords

Search

Navigation