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CC BY 4.0 · Pharmaceutical Fronts 2024; 06(04): e439-e448
DOI: 10.1055/s-0044-1791832
Original Article

Resveratrol-Loaded Dissolving Microneedles: Fabrication and in vitro Evaluation

Banghuai Xing
1   Division of Innovative Pharmaceutical Sciences, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China
,
Qian Luo
1   Division of Innovative Pharmaceutical Sciences, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China
,
Tiantian Gan
1   Division of Innovative Pharmaceutical Sciences, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China
,
Yi Jin
1   Division of Innovative Pharmaceutical Sciences, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China
,
Jianfang Feng
1   Division of Innovative Pharmaceutical Sciences, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China
2   Department of Pharmaceutical Sciences, School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, People's Republic of China
,
Meng Cheng
3   GCP Center, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, People's Republic of China
,
Liangxing Tu
1   Division of Innovative Pharmaceutical Sciences, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China
› Author Affiliations Funding This research was funded by the Natural Science Foundation of Jiangxi Province (Grant No. 20242BAB23090), the Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program (Grant Nos. CXTD-22008, CXTD-22004), the PhD startup foundation of Affiliated Hospital of Jiangxi University of Chinese Medicine (Grant No. 23KYQDZJ02) and the students' innovation and entrepreneurship training program (Grant Nos. 202110412009, 202210412312).
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Abstract

Resveratrol (Res), an active ingredient derived from a multitude of plants, exhibits multiple pharmacological activities. However, its poor water solubility and low bioavailability present significant challenges to its clinical application. Our study aimed to improve the transdermal absorption of Res using dissolving microneedle (MN) technology, which could effectively overcome the stratum corneum barrier. Res-loaded dissolving microneedles (Res-MNs) were fabricated using polyvinyl pyrrolidone K90 (PVP K90) as the matrix material, and a two-step casting procedure was employed. The process was optimized using the Box–Behnken experimental design approach. The characteristics of Res-MNs in vitro, including morphology, solubility, safety evaluation, and skin permeation, were studied. The results showed that the optimum preparation conditions of Res-MNs were a centrifugation time of 10 minutes, a solvent concentration of 25%, and a prescription ratio (Res: matrix) of 0.375. The skin permeability of the Res-MNs was enhanced compared with Res suspension and Res gel. The cumulative release of Res-MNs in vitro was 75%, which was approximately 5 and 3 times that of the Res suspension group and Res gel group. These results suggest that dissolving MNs may represent a potential approach for enhancing the transdermal delivery of poorly absorbed drugs such as Res.

Keywords

microneedle - transdermal - resveratrol - absorption - polyvinylpyrrolidone K90

Ethical Approval

This work was approved by the Animal Ethics Committee and abides by the relevant agreements of the National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine.




Publication History

Received: 22 November 2023

Accepted: 24 September 2024

Article published online:
08 November 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Ren J, Liu H, Hao Y, He P, Fang Y. Determination of resveratrol in red wine by solid phase extraction-flow injection chemiluminescence method. Chin Chem Lett 2007; 18: 985-988
    CrossrefSearch in Google Scholar
  • 2 Zhang Q, Bian Y, Shi Y. et al. An economical and efficient technology for the extraction of resveratrol from peanut (Arachis hypogaea) sprouts by multi-stage countercurrent extraction. Food Chem 2015; 179: 15-25
    CrossrefPubMedSearch in Google Scholar
  • 3 Ros E, Singh A, O'Keefe JH. Nuts: natural pleiotropic nutraceuticals. Nutrients 2021; 13 (09) 3269
    CrossrefPubMedSearch in Google Scholar
  • 4 Abdel Bar FM, Abbas GM, Gohar AA, Lahloub MI. Antiproliferative activity of stilbene derivatives and other constituents from the stem bark of Morus nigra L. Nat Prod Res 2020; 34 (24) 3506-3513
    CrossrefPubMedSearch in Google Scholar
  • 5 Ungurianu A, Zanfirescu A, Margină D. Sirtuins, resveratrol and the intertwining cellular pathways connecting them. Ageing Res Rev 2023; 88: 101936
    CrossrefPubMedSearch in Google Scholar
  • 6 Chedea VS, Vicaş SI, Sticozzi C. et al. Resveratrol: from diet to topical usage. Food Funct 2017; 8 (11) 3879-3892
    CrossrefPubMedSearch in Google Scholar
  • 7 Cho S, Namkoong K, Shin M. et al. Cardiovascular protective effects and clinical applications of resveratrol. J Med Food 2017; 20 (04) 323-334
    CrossrefPubMedSearch in Google Scholar
  • 8 Ko JH, Sethi G, Um JY. et al. The role of resveratrol in cancer therapy. Int J Mol Sci 2017; 18 (12) 2589
    CrossrefPubMedSearch in Google Scholar
  • 9 Kotecha R, Takami A, Espinoza JL. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence. Oncotarget 2016; 7 (32) 52517-52529
    CrossrefPubMedSearch in Google Scholar
  • 10 Nawaz W, Zhou Z, Deng S. et al. Therapeutic versatility of resveratrol derivatives. Nutrients 2017; 9 (11) 1188
    CrossrefPubMedSearch in Google Scholar
  • 11 Tang H, Xiang S, Li X, Zhou J, Kuang C. Preparation and in vitro performance evaluation of resveratrol for oral self-microemulsion. PLoS One 2019; 14 (04) e0214544
    CrossrefPubMedSearch in Google Scholar
  • 12 Annaji M, Poudel I, Boddu SHS, Arnold RD, Tiwari AK, Babu RJ. Resveratrol-loaded nanomedicines for cancer applications. Cancer Rep (Hoboken) 2021; 4 (03) e1353
    CrossrefPubMedSearch in Google Scholar
  • 13 Tosato MG, Maya Girón JV, Martin AA, Krishna Tippavajhala V, Fernández Lorenzo de Mele M, Dicelio L. Comparative study of transdermal drug delivery systems of resveratrol: high efficiency of deformable liposomes. Mater Sci Eng C 2018; 90: 356-364
    CrossrefPubMedSearch in Google Scholar
  • 14 Sinha D, Sarkar N, Biswas J, Bishayee A. Resveratrol for breast cancer prevention and therapy: preclinical evidence and molecular mechanisms. Semin Cancer Biol 2016; 40-41: 209-232
    CrossrefPubMedSearch in Google Scholar
  • 15 Pujara N, Jambhrunkar S, Wong KY, McGuckin M, Popat A. Enhanced colloidal stability, solubility and rapid dissolution of resveratrol by nanocomplexation with soy protein isolate. J Colloid Interface Sci 2017; 488: 303-308
    CrossrefPubMedSearch in Google Scholar
  • 16 Qu F, Geng R, Liu Y, Zhu J. Advanced nanocarrier- and microneedle-based transdermal drug delivery strategies for skin diseases treatment. Theranostics 2022; 12 (07) 3372-3406
    CrossrefPubMedSearch in Google Scholar
  • 17 Zhang Y, Liu C, Wang JQ. et al. Ionic liquids in transdermal drug delivery system: current applications and future perspectives. Chin Chem Lett 2023; 34: 107631
    CrossrefSearch in Google Scholar
  • 18 Alany R. Topical and transdermal formulation and drug delivery. Pharm Dev Technol 2017; 22 (04) 457
    CrossrefPubMedSearch in Google Scholar
  • 19 Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol 2008; 26 (11) 1261-1268
    CrossrefPubMedSearch in Google Scholar
  • 20 Dharadhar S, Majumdar A, Dhoble S, Patravale V. Microneedles for transdermal drug delivery: a systematic review. Drug Dev Ind Pharm 2019; 45 (02) 188-201
    CrossrefPubMedSearch in Google Scholar
  • 21 Zhang X, Wang Y, Chi J, Zhao Y. Smart microneedles for therapy and diagnosis. Research (Wash D C) 2020; 2020: 7462915
    PubMedSearch in Google Scholar
  • 22 Zuo J, Du L, Li M, Liu B, Zhu W, Jin Y. Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs. Int J Pharm 2014; 466 (1-2): 76-82
    CrossrefPubMedSearch in Google Scholar
  • 23 Andrade JFM, Cunha-Filho M, Gelfuso GM, Gratieri T. Iontophoresis for the cutaneous delivery of nanoentraped drugs. Expert Opin Drug Deliv 2023; 20 (06) 785-798
    CrossrefPubMedSearch in Google Scholar
  • 24 Seah BC, Teo BM. Recent advances in ultrasound-based transdermal drug delivery. Int J Nanomedicine 2018; 13: 7749-7763
    CrossrefPubMedSearch in Google Scholar
  • 25 Sammeta SM, Repka MA, Narasimha Murthy S. Magnetophoresis in combination with chemical enhancers for transdermal drug delivery. Drug Dev Ind Pharm 2011; 37 (09) 1076-1082
    CrossrefPubMedSearch in Google Scholar
  • 26 Huang D, Huang Y, Li Z. Transdermal delivery of nucleic acid-mediated by punching and electroporation. Methods Mol Biol 2020; 2050: 101-112
    CrossrefPubMedSearch in Google Scholar
  • 27 Zhang H, Jin WR. Determination of amino acids in an individual erythrocyteby capillary electrophoresis with intracellular FITC-derivatization and laser-induced fluorescence detection. Chin Chem Lett 2003; 14: 952-954
    Search in Google Scholar
  • 28 Dradrach K, Rogóż M, Grabowski P. et al. Traveling wave rotary micromotor based on a photomechanical response in liquid crystal polymer networks. ACS Appl Mater Interfaces 2020; 12 (07) 8681-8686
    CrossrefPubMedSearch in Google Scholar
  • 29 Sharma D. Microneedles: an approach in transdermal drug delivery: a review. Pharmatutor 2018; 6: 07
    CrossrefSearch in Google Scholar
  • 30 Ali MK, Moshikur RM, Goto M, Moniruzzaman M. Recent developments in ionic liquid-assisted topical and transdermal drug delivery. Pharm Res 2022; 39 (10) 2335-2351
    CrossrefPubMedSearch in Google Scholar
  • 31 Park D, Won J, Lee G, Lee Y, Kim CW, Seo J. Sonophoresis with ultrasound-responsive liquid-core nuclei for transdermal drug delivery. Skin Res Technol 2022; 28 (02) 291-298
    CrossrefPubMedSearch in Google Scholar
  • 32 Chen Z, Lv Y, Qi J, Zhu Q, Lu Y, Wu W. Overcoming or circumventing the stratum corneum barrier for efficient transcutaneous immunization. Drug Discov Today 2018; 23 (01) 181-186
    CrossrefPubMedSearch in Google Scholar
  • 33 Pireddu R, Schlich M, Marceddu S. et al. Nanosuspensions and microneedles roller as a combined approach to enhance diclofenac topical bioavailability. Pharmaceutics 2020; 12 (12) 1140
    CrossrefPubMedSearch in Google Scholar
  • 34 Sheng T, Luo B, Zhang W. et al. Microneedle-mediated vaccination: innovation and translation. Adv Drug Deliv Rev 2021; 179: 113919
    CrossrefPubMedSearch in Google Scholar
  • 35 Ramaut L, Hoeksema H, Pirayesh A, Stillaert F, Monstrey S. Microneedling: where do we stand now? A systematic review of the literature. J Plast Reconstr Aesthet Surg 2018; 71 (01) 1-14
    CrossrefPubMedSearch in Google Scholar
  • 36 Kapoor Y, Milewski M, Dick L. et al. Coated microneedles for transdermal delivery of a potent pharmaceutical peptide. Biomed Microdevices 2019; 22 (01) 7
    CrossrefPubMedSearch in Google Scholar
  • 37 Chen Z, He J, Qi J, Zhu Q, Wu W, Lu Y. Long-acting microneedles: a progress report of the state-of-the-art techniques. Drug Discov Today 2020; 25 (08) 1462-1468
    CrossrefPubMedSearch in Google Scholar
  • 38 Tan JY, Li Y, Chamani F. et al. Experimental validation of diffraction lithography for fabrication of solid microneedles. Materials (Basel) 2022; 15 (24) 8934
    CrossrefPubMedSearch in Google Scholar
  • 39 Cárcamo-Martínez Á, Mallon B, Domínguez-Robles J, Vora LK, Anjani QK, Donnelly RF. Hollow microneedles: a perspective in biomedical applications. Int J Pharm 2021; 599: 120455
    CrossrefPubMedSearch in Google Scholar
  • 40 Matadh AV, Jakka D, Pragathi SG. et al. Polymer-coated polymeric (PCP) microneedles for controlled dermal delivery of 5-fluorouracil. AAPS PharmSciTech 2022; 24 (01) 9
    CrossrefPubMedSearch in Google Scholar
  • 41 Sartawi Z, Blackshields C, Faisal W. Dissolving microneedles: applications and growing therapeutic potential. J Control Release 2022; 348: 186-205
    CrossrefPubMedSearch in Google Scholar
  • 42 Liu Y, Huang T, Qian ZY, Chen W. Extensible and swellable hydrogel-forming microneedles for deep point-of-care sampling and drug deployment. Chin Chem Lett 2023; 34: 108103
    CrossrefSearch in Google Scholar
  • 43 Ita K. Dissolving microneedles for transdermal drug delivery: advances and challenges. Biomed Pharmacother 2017; 93: 1116-1127
    CrossrefPubMedSearch in Google Scholar
  • 44 Sullivan SP, Koutsonanos DG, Del Pilar Martin M. et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med 2010; 16 (08) 915-920
    CrossrefPubMedSearch in Google Scholar
  • 45 Ronnander P, Simon L, Koch A. Experimental and mathematical study of the transdermal delivery of sumatriptan succinate from polyvinylpyrrolidone-based microneedles. Eur J Pharm Biopharm 2020; 146: 32-40
    CrossrefPubMedSearch in Google Scholar
  • 46 Song YY, Dong CM. Sugar-dependent targeting and immune adjuvant effects of hyperbranched glycosylated polypeptide nanoparticles for ovalbumin delivery. Chin Chem Lett 2022; 33: 4084-4088
    CrossrefSearch in Google Scholar
  • 47 Nguyen HX, Bozorg BD, Kim Y. et al. Poly (vinyl alcohol) microneedles: fabrication, characterization, and application for transdermal drug delivery of doxorubicin. Eur J Pharm Biopharm 2018; 129: 88-103
    CrossrefPubMedSearch in Google Scholar
  • 48 Wu L, Shrestha P, Iapichino M, Cai Y, Kim B, Stoeber B. Characterization method for calculating diffusion coefficient of drug from polylactic acid (PLA) microneedles into the skin. J Drug Deliv Transl 2021; 61: 102192
    Search in Google Scholar
  • 49 He J, Zhang Z, Zheng X. et al. Design and evaluation of dissolving microneedles for enhanced dermal delivery of propranolol hydrochloride. Pharmaceutics 2021; 13 (04) 579
    CrossrefPubMedSearch in Google Scholar
  • 50 Maurya A, Nanjappa SH, Honnavar S, Salwa M, Murthy SN. Rapidly dissolving microneedle patches for transdermal iron replenishment therapy. J Pharm Sci 2018; 107 (06) 1642-1647
    CrossrefPubMedSearch in Google Scholar
  • 51 Pei P, Yang F, Liu J. et al. Composite-dissolving microneedle patches for chemotherapy and photothermal therapy in superficial tumor treatment. Biomater Sci 2018; 6 (06) 1414-1423
    CrossrefPubMedSearch in Google Scholar
  • 52 Ahmed Saeed Al-Japairai K, Mahmood S, Hamed Almurisi S. et al. Current trends in polymer microneedle for transdermal drug delivery. Int J Pharm 2020; 587: 119673
    CrossrefPubMedSearch in Google Scholar
  • 53 Hong X, Wei L, Wu F. et al. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des Devel Ther 2013; 7: 945-952
    PubMedSearch in Google Scholar
  • 54 Zhang L, Dong Z, Liu W. et al. Novel Pharmaceutical strategies for enhancing skin penetration of biomacromolecules. Pharmaceuticals (Basel) 2022; 15 (07) 877
    CrossrefPubMedSearch in Google Scholar
  • 55 Chen YH, Lin DC, Chern E, Huang YY. The use of micro-needle arrays to deliver cells for cellular therapies. Biomed Microdevices 2020; 22 (04) 63
    CrossrefPubMedSearch in Google Scholar
  • 56 Yang H, Kang G, Jang M. et al. Development of lidocaine-loaded dissolving microneedle for rapid and efficient local anesthesia. Pharmaceutics 2020; 12 (11) 1067
    CrossrefPubMedSearch in Google Scholar
  • 57 Yu Q, Huang Y, Zhu C. et al. Combination of microneedles and MF59 adjuvant as a simple approach to enhance transcutaneous immunization. J Biomed Nanotechnol 2020; 16 (12) 1776-1786
    CrossrefPubMedSearch in Google Scholar
  • 58 Dalvi M, Kharat P, Thakor P, Bhavana V, Singh SB, Mehra NK. Panorama of dissolving microneedles for transdermal drug delivery. Life Sci 2021; 284: 119877
    CrossrefPubMedSearch in Google Scholar
  • 59 Cheng M, Yuan F, Liu J. et al. Fabrication of fine puerarin nanocrystals by Box-Behnken design to enhance intestinal absorption. AAPS PharmSciTech 2020; 21 (03) 90
    CrossrefPubMedSearch in Google Scholar
  • 60 Rouphael NG, Paine M, Mosley R. et al; TIV-MNP 2015 Study Group. The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Lancet 2017; 390 (10095): 649-658
    CrossrefPubMedSearch in Google Scholar
  • 61 Van Damme P, Oosterhuis-Kafeja F, Van der Wielen M, Almagor Y, Sharon O, Levin Y. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine 2009; 27 (03) 454-459
    CrossrefPubMedSearch in Google Scholar
  • 62 Chatterjee B, Reddy A, Santra M, Khamanga S. Amorphization of drugs for transdermal delivery-a recent update. Pharmaceutics 2022; 14 (05) 983
    CrossrefPubMedSearch in Google Scholar
  • 63 Yoon DS, Choi Y, Jang Y. et al. SIRT1 directly regulates SOX2 to maintain self-renewal and multipotency in bone marrow-derived mesenchymal stem cells. Stem Cells 2014; 32 (12) 3219-3231
    CrossrefPubMedSearch in Google Scholar
  • 64 Qiang N, Liu Z, Lu M. et al. Preparation and properties of polyvinylpyrrolidone/sodium carboxymethyl cellulose soluble microneedles. Materials (Basel) 2023; 16 (09) 3417
    CrossrefPubMedSearch in Google Scholar
  • 65 Aung NN, Ngawhirunpat T, Rojanarata T, Patrojanasophon P, Opanasopit P, Pamornpathomkul B. HPMC/PVP dissolving microneedles: a promising delivery platform to promote trans-epidermal delivery of alpha-arbutin for skin lightening. AAPS PharmSciTech 2019; 21 (01) 25
    CrossrefPubMedSearch in Google Scholar
  • 66 Wang Q, Yao G, Dong P. et al. Investigation on fabrication process of dissolving microneedle arrays to improve effective needle drug distribution. Eur J Pharm Sci 2015; 66: 148-156
    CrossrefPubMedSearch in Google Scholar
  • 67 Al-Saidan SM, Krishnaiah YS, Chandrasekhar DV. et al. Formulation of an HPMC gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing in vitro transdermal delivery of nicorandil. Skin Pharmacol Physiol 2004; 17 (06) 310-320
    CrossrefPubMedSearch in Google Scholar
  • 68 Kovačević M, Zvonar Pobirk A, German Ilić I. The effect of polymeric binder type and concentration on flow and dissolution properties of SMEDDS loaded mesoporous silica-based granules. Eur J Pharm Sci 2024; 193: 106582
    CrossrefPubMedSearch in Google Scholar
  • 69 Du H, Liu P, Zhu J. et al. Hyaluronic acid-based dissolving microneedle patch loaded with methotrexate for improved treatment of psoriasis. ACS Appl Mater Interfaces 2019; 11 (46) 43588-43598
    CrossrefPubMedSearch in Google Scholar
  • 70 Waghule T, Singhvi G, Dubey SK. et al. Microneedles: a smart approach and increasing potential for transdermal drug delivery system. Biomed Pharmacother 2019; 109: 1249-1258
    CrossrefPubMedSearch in Google Scholar
  • 71 Bala P, Jathar S, Kale S. et al. Transdermal drug delivery system (TDDS)-a multifaceted approach for drug delivery. J Pharm Res 2014; 8 (12) 1805-1835
    Search in Google Scholar