Polymeric and Composite-based Microneedles in Drug Delivery: Regenerative Medicine, Microbial Infection Therapy, and Cancer Treatment

Document Type : Review Article

Authors

1 Research Laboratory of Spectrometry & Micro and Nano Extraction, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran

2 Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Microneedles (MNs) are microscopic, needle-like structures employed in drug delivery through the skin. They are non-invasive and cause minimal to no pain at the site of insertion into the skin. MNs can be used to successfully deliver both small and large molecules to people who need them. Polymeric MNs have recently been combined with nanomaterials in order to construct flexible nanocomposite systems, allowing their use in biomedicine to be expanded. The literature has provided in-depth evaluations of MN patch technology, which has led to a dramatic rise in the number of scholarly articles on this topic. This review introduces different nanocomposite-based MN applications in the fields of tissue regeneration, microbial infection, and cancer therapy. Also, the prospects and challenges of nanocomposite-based MNs are briefly discussed.
 
 

Graphical Abstract

Polymeric and Composite-based Microneedles in Drug Delivery: Regenerative Medicine, Microbial Infection Therapy, and Cancer Treatment

Keywords


 [1] G. Yang, Q. Chen, D. Wen, Z. Chen, J. Wang, G. Chen, Z. Wang, X. Zhang, Y. Zhang, Q. Hu, A therapeutic microneedle patch made from hair-derived keratin for promoting hair regrowth, ACS Nano 13(4) (2019) 4354-4360.
[2] Z. Wang, J. Zhao, W. Tang, L. Hu, X. Chen, Y. Su, C. Zou, J. Wang, W.W. Lu, W. Zhen, Multifunctional nanoengineered
hydrogels consisting of black phosphorus nanosheets upregulate bone formation, Small 15(41) (2019) 1901560.
[3] M. Wang, Y. Han, X. Yu, L. Liang, H. Chang, D.C. Yeo, C. Wiraja, M.L. Wee, L. Liu, X. Liu, Upconversion nanoparticle
powered microneedle patches for transdermal delivery of siRNA, Adv. Healthc. Mater. 9(2) (2020) 1900635.
[4] Y. Zhao, W. Ran, J. He, Y. Huang, Z. Liu, W. Liu, Y. Tang, L. Zhang, D. Gao, F. Gao, High
performance asymmetric
supercapacitors based on multilayer MnO
2/graphene oxide nanoflakes and hierarchical porous carbon with enhanced cycling stability, Small 11(11) (2015) 1310-1319.
[5] C. Su, Y. Chen, S. Tian, C. Lu, Q. Lv, Research Progress on Emerging Polysaccharide Materials Applied in Tissue Engineering, Polymers 14(16) (2022) 3268.
[6] K. Van Der Maaden, W. Jiskoot, J. Bouwstra, Microneedle technologies for (trans) dermal drug and vaccine delivery, J.Control. Release 161(2) (2012) 645-655.
[7] A. Malek-Khatabi, Z.F. Rad, M. Rad-Malekshahi, H. Akbarijavar, Development of dissolvable microneedle patches by CNC machining and micromolding for drug delivery, Mater. Lett. 330 (2023) 133328.
[8] N.W. Kim, S.-Y. Kim, J.E. Lee, Y. Yin, J.H. Lee, S.Y. Lim, E.S. Kim, H.T.T. Duong, H.K. Kim, S. Kim, Enhanced cancer
vaccination by in situ nanomicelle-generating dissolving microneedles, ACS Nano 12(10) (2018) 9702-9713.
[9] A. Malek-Khatabi, Z. Tabandeh, A. Nouri, E. Mozayan, R. Sartorius, S. Rahimi, R. Jamaledin, Long-Term Vaccine Delivery
and Immunological Responses Using Biodegradable Polymer-Based Carriers, ACS Appl. Bio Mater. 5(11) (2022) 5015-5040.
[10] L. Yan, A.P. Raphael, X. Zhu, B. Wang, W. Chen, T. Tang, Y. Deng, H.J. Sant, G. Zhu, K.W. Choy, Nanocomposite

strengthened dissolving microneedles for improved transdermal delivery to human skin, Adv. Healthc. Mater. 3(4) (2014) 555- 564.
[11] F. Song, X. Li, Q. Wang, L. Liao, C. Zhang, Nanocomposite hydrogels and their applications in drug delivery and tissue
engineering, J. Biomed. Nanotechnol 11(1) (2015) 40-52.
[12] R. Parhi, Nanocomposite for transdermal drug delivery, Applications of nanocomposite materials in drug delivery,
Elsevier2018, pp. 353-389.
[13] C.H. Park, T. Kim, G.H. Lee, K.H. Ku, S.-H. Kim, B.J. Kim, Fluorescent Polymer-MoS2-Embedded Microgels for
Photothermal Heating and Colorimetric Monitoring, ACS Appl. Mater. Interfaces. 12(31) (2020) 35415-35423.
[14] R. Samanipour, T. Wang, M. Werb, H. Hassannezhad, J.M. Ledesma Rangel, M. Hoorfar, A. Hasan, C.K. Lee, S.R. Shin,
Ferritin nanocage conjugated hybrid hydrogel for tissue engineering and drug delivery applications, ACS Biomater. Sci. Eng. 6(1) (2019) 277-287.
[15] W. Zhao, K. Odelius, U. Edlund, C. Zhao, A.-C. Albertsson, In situ synthesis of magnetic field-responsive hemicellulose
hydrogels for drug delivery, Biomacromolecules 16(8) (2015) 2522-2528.
[16] S.P. Sullivan, D.G. Koutsonanos, M. del Pilar Martin, J.W. Lee, V. Zarnitsyn, S.-O. Choi, N. Murthy, R.W. Compans, I.
Skountzou, M.R. Prausnitz, Dissolving polymer microneedle patches for influenza vaccination, Nat. Med. 16(8) (2010) 915-
920.
[17] C.-J. Ke, Y.-J. Lin, Y.-C. Hu, W.-L. Chiang, K.-J. Chen, W.-C. Yang, H.-L. Liu, C.-C. Fu, H.-W. Sung, Multidrug release
based on microneedle arrays filled with pH-responsive PLGA hollow microspheres, Biomaterials 33(20) (2012) 5156-5165.
[18] J.W. Lee, J.-H. Park, M.R. Prausnitz, Dissolving microneedles for transdermal drug delivery, Biomaterials 29(13) (2008)
2113-2124.
[19] P. Makvandi, M. Shabani, N. Rabiee, Q.K. Anjani, A. Maleki, E.N. Zare, A.H.B. Sabri, D. De Pasquale, M. Koskinopoulou,
E. Sharifi, Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug
Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to ex vivo and in vivo Tissues, Adv. Mater. (2023) 2210034.
[20] R. Justin, B. Chen, Strong and conductive chitosan–reduced graphene oxide nanocomposites for transdermal drug delivery, J. Mater. Chem. B. 2(24) (2014) 3759-3770.
[21] Y. Piao, B. Chen, Self
assembled graphene oxide–gelatin nanocomposite hydrogels: Characterization, formation mechanisms, and pHsensitive drug release behavior, J. Polym. Sci., Part B: Polym. Phys. 53(5) (2015) 356-367.
[22] R. Justin, B. Chen, Characterisation and drug release performance of biodegradable chitosan–graphene oxide nanocomposites, Carbohydr. Polym. 103 (2014) 70-80.
[23] K. Kabashima, T. Honda, F. Ginhoux, G. Egawa, The immunological anatomy of the skin, Nature reviews. Immunology 19(1) (2019) 19-30.
[24] Y.E. Chen, M.A. Fischbach, Y. Belkaid, Skin microbiota–host interactions, Nature 553(7689) (2018) 427-436.
[25] R.F. Donnelly, T.R.R. Singh, M.M. Tunney, D.I. Morrow, P.A. McCarron, C. O’Mahony, A.D. Woolfson, Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro, Pharm. Res. 26(11) (2009) 2513-2522.
[26] F. Zhang, Q. Zhang, X. Li, N. Huang, X. Zhao, Z. Yang, Mussel-inspired dopamine-CuII coatings for sustained in situ
generation of nitric oxide for prevention of stent thrombosis and restenosis, Biomaterials 194 (2019) 117-129.
[27] S. Baik, D.W. Kim, Y. Park, T.-J. Lee, S. Ho Bhang, C. Pang, A wet-tolerant adhesive patch inspired by protuberances in
suction cups of octopi, Nature 546(7658) (2017) 396-400.
[28] P. Makvandi, A. Maleki, M. Shabani, A.R. Hutton, M. Kirkby, R. Jamaledin, T. Fang, J. He, J. Lee, B. Mazzolai, Bioinspired
microneedle patches: Biomimetic designs, fabrication, and biomedical applications, Matter 5(2) (2022) 390-429.
[29] R. Jamaledin, C.K. Yiu, E.N. Zare, L.N. Niu, R. Vecchione, G. Chen, Z. Gu, F.R. Tay, P. Makvandi, Advances in antimicrobial microneedle patches for combating infections, Adv. Mater. 32(33) (2020) 2002129.
[30] D.R. Cranendonk, F. Hugenholtz, J.M. Prins, P.H. Savelkoul, A.E. Budding, W.J. Wiersinga, The skin microbiota in patients hospitalized for cellulitis and association with outcome, Clin. Infect. Dis. 68(8) (2019) 1292-1299.
[31] P. Makvandi, R. Jamaledin, M. Jabbari, N. Nikfarjam, A. Borzacchiello, Antibacterial quaternary ammonium compounds in dental materials: A systematic review, Dent. Mater. J. 34(6) (2018) 851-867.
[32] M. Delfi, M. Ghomi, A. Zarrabi, R. Mohammadinejad, Z.B. Taraghdari, M. Ashrafizadeh, E.N. Zare, T. Agarwal, V.V. Padil,
B. Mokhtari, Functionalization of Polymers and Nanomaterials for Biomedical Applications: Antimicrobial Platforms and Drug Carriers, PROSTHESIS 2(2) (2020) 117-139.
[33] P. Makvandi, G.W. Ali, F. Della Sala, W.I. Abdel-Fattah, A. Borzacchiello, Biosynthesis and characterization of antibacterial thermosensitive hydrogels based on corn silk extract, hyaluronic acid and nanosilver for potential wound healing, Carbohydr. Polym. 223 (2019) 115023.
[34] S.J. Lam, E.H. Wong, C. Boyer, G.G. Qiao, Antimicrobial polymeric nanoparticles, Prog. Polym. Sci. 76 (2018) 40-64.
[35] F. Wang, X. Zhang, G. Chen, Y. Zhao, Living bacterial microneedles for fungal infection treatment, Research 2020 (2020) 2760594.
[36] J. Xu, R. Danehy, H. Cai, Z. Ao, M. Pu, A. Nusawardhana, D. Rowe-Magnus, F. Guo, Microneedle patch-mediated treatment of bacterial biofilms, ACS Appl. Mater. Interfaces. 11(16) (2019) 14640-14646.
[37] R. Sachan, P. Jaipan, J.Y. Zhang, S. Degan, D. Erdmann, J. Tedesco, L. Vanderwal, S.J. Stafslien, I. Negut, A. Visan, Printing amphotericin B on microneedles using matrix-assisted pulsed laser evaporation, Int. J. Bioprinting 3(2) (2017) 004.
[38] H.S. Lee, H.R. Ryu, J.Y. Roh, J.-H. Park, Bleomycin-coated microneedles for treatment of warts, Pharm. Res. 34(1) (2017) 101-112.
[39] T. Waghule, G. Singhvi, S.K. Dubey, M.M. Pandey, G. Gupta, M. Singh, K. Dua, Microneedles: A smart approach and
increasing potential for transdermal drug delivery system, Biomed. Pharmacother. 109 (2019) 1249-1258.
[40] H.A. Benson, J.E. Grice, Y. Mohammed, S. Namjoshi, M.S. Roberts, Topical and transdermal drug delivery: from simple
potions to smart technologies, Curr. Drug Deliv. 16(5) (2019) 444-460.
[41] J. Chi, X. Zhang, C. Chen, C. Shao, Y. Zhao, Y. Wang, Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing, Bioact. Mater. 5(2) (2020) 253-259.
[42] C.E. Krewson, M.L. Klarman, W.M. Saltzman, Distribution of nerve growth factor following direct delivery to brain
interstitium, Brain Res. 680(1-2) (1995) 196-206.
[43] M.J. Mahoney, W.M. Saltzman, Controlled release of proteins to tissue transplants for the treatment of neurodegenerative disorders, J. Pharm. Sci. 85(12) (1996) 1276-1281.
[44] A.S. Rzhevskiy, T.R.R. Singh, R.F. Donnelly, Y.G. Anissimov, Microneedles as the technique of drug delivery enhancement in diverse organs and tissues, J. Control. Release 270 (2018) 184-202.
[45] C.K. Choi, J.B. Kim, E.H. Jang, Y.N. Youn, W.H. Ryu, Curved biodegradable microneedles for vascular drug delivery, Small 8(16) (2012) 2483-2488.
[46] K. Lee, Y. Xue, J. Lee, H.J. Kim, Y. Liu, P. Tebon, E. Sarikhani, W. Sun, S. Zhang, R. Haghniaz, A patch of detachable hybrid microneedle depot for localized delivery of mesenchymal stem cells in regeneration therapy, Adv. Funct. Mater. 30(23) (2020) 2000086.
[47] J. Chi, L. Sun, L. Cai, L. Fan, C. Shao, L. Shang, Y. Zhao, Chinese herb microneedle patch for wound healing, Bioact. Mater. 6(10) (2021) 3507-3514.
[48] M.R. Prausnitz, Microneedles for transdermal drug delivery, Adv. Drug Deliv. Rev. 56(5) (2004) 581-587.
[49] A. Doraiswamy, C. Jin, R. Narayan, P. Mageswaran, P. Mente, R. Modi, R. Auyeung, D. Chrisey, A. Ovsianikov, B. Chichkov, Two photon induced polymerization of organic–inorganic hybrid biomaterials for microstructured medical devices, Acta Biomater. 2(3) (2006) 267-275.
[50] A.J. Mellott, M.L. Forrest, M.S. Detamore, Physical non-viral gene delivery methods for tissue engineering, Ann. Biomed. Eng . 41(3) (2013) 446-468.
[51] F. Yamamoto, M. Furusawa, I. Furusawa, M. Obinata, The ‘pricking’method: A new efficient technique for mechanically
introducing foreign DNA into the nuclei of culture cells, Exp. Cell Res. 142(1) (1982) 79-84.
[52] J.K. Cinkornpumin, R.L. Hong, RNAi mediated gene knockdown and transgenesis by microinjection in the necromenic
nematode Pristionchus pacificus, J. Vis. Exp. (56) (2011) e3270.
[53] M. Dahlhoff, M. Grzech, F.A. Habermann, E. Wolf, M.R. Schneider, A transgenic mouse line expressing cre recombinase in pancreatic
β‐cells, Gen. 50(5) (2012) 437-442.
[54] Y. Zhao, S. Song, X. Ren, J. Zhang, Q. Lin, Y. Zhao, Supramolecular Adhesive Hydrogels for Tissue Engineering
Applications, Chem. Rev. 122(6) (2022) 5604-5640.
[55] S. Nadine, A. Chung, S.E. Diltemiz, B. Yasuda, C. Lee, V. Hosseini, S. Karamikamkar, N.R. de Barros, K. Mandal, S. Advani, Advances in microfabrication technologies in tissue engineering and regenerative medicine, Artif. Organs. 46 (7) (2022) 211- 243.
[56] S.P. Grogan, E.W. Dorthé, N.E. Glembotski, F. Gaul, D.D. D’Lima, Cartilage tissue engineering combining microspheroid building blocks and microneedle arrays, Connect. Tissue Res. 61(2) (2020) 229-243.
[57] N.I. Moldovan, N. Hibino, K. Nakayama, Principles of the Kenzan method for robotic cell spheroid-based three-dimensional bioprinting, Tissue Eng. Part B Rev. 23(3) (2017) 237-244.
[58] D. Murata, K. Arai, K. Nakayama, Scaffold
free bio3D printing using spheroids as “bioinks” for tissue (Re) construction and drug response tests, Adv. Healthc. Mater. 9(15) (2020) 1901831.
[59] H.-J. Jeong, H. Nam, J. Jang, S.-J. Lee, 3D bioprinting strategies for the regeneration of functional tubular tissues and organs, Bioeng. 7(2) (2020) 32.
[60] K. Prashant, H.E. Ivan, M. El-Sayed, Au nanoparticles target cancer, Nano Today 2(1) (2007) 18-29.
[61] L.A. Nalone, R.G. Amaral, D.M. de Lima Oliveira, L.R. Andrade, L.M. de Hollanda, C.F. da Silva, E.B. Souto, P. Severino,
Applications of nanocomposite materials in the delivery of anticancer drugs, Applications of nanocomposite materials in drug delivery, Elsevier2018, pp. 339-352.
[62] L. Li, G. Takemura, Y. Li, S. Miyata, M. Esaki, H. Okada, H. Kanamori, A. Ogino, R. Maruyama, M. Nakagawa, Granulocyte colony-stimulating factor improves left ventricular function of doxorubicin-induced cardiomyopathy, Lab. Invest. 87(5) (2007) 440-455.
[63] Y. Zhu, C. Tao, DNA-capped Fe 3 O 4/SiO 2 magnetic mesoporous silica nanoparticles for potential controlled drug release and hyperthermia, RSC Adv. 5(29) (2015) 22365-22372.
[64] W. Sang, Z. Zhang, Y. Dai, X. Chen, Recent advances in nanomaterial-based synergistic combination cancer immunotherapy, Chem. Soc. Rev. 48(14) (2019) 3771-3810.
[65] D. Rosenblum, N. Joshi, W. Tao, J.M. Karp, D. Peer, Progress and challenges towards targeted delivery of cancer therapeutics, Nat. Commun. 9(1) (2018) 1-12.
[66] C.F. Rodrigues, T.A. Jacinto, A.F. Moreira, E.C. Costa, S.P. Miguel, I.J. Correia, Functionalization of AuMSS nanorods
towards more effective cancer therapies, Nano Res. 12(4) (2019) 719-732.
[67] P. Pei, F. Yang, J. Liu, H. Hu, X. Du, N. Hanagata, S. Zhao, Y. Zhu, Composite-dissolving microneedle patches for
chemotherapy and photothermal therapy in superficial tumor treatment, Biomater. Sci. 6(6) (2018) 1414-1423.
[68] Z. Zhang, W. Li, D. Chang, Z. Wei, E. Wang, J. Yu, Y. Xu, Y. Que, Y. Chen, C. Fan, A combination therapy for androgenic
alopecia based on quercetin and zinc/copper dual-doped mesoporous silica nanocomposite microneedle patch, Bioact. Mater. 24 (2023) 81-95.