Main Article Content

Marjan Sobhanieh
Alireza Ghadian


Microbubbles, microswimmers, drug delivery, imaging, gastrointestinal tract


The gastrointestinal (GI) tract presents challenges for drug delivery and imaging due to its harsh conditions. Microbubbles and microswimmers have emerged as promising strategies to overcome these challenges. Microbubbles are gas-filled bubbles that can be functionalized with drugs and imaging agents, while microswimmers are self-propelled objects that can navigate through the GI
tract. This review provides an overview of microbubble and microswimmer technology in GI tract drug delivery and imaging. It discusses their potential applications, advantages, and limitations compared to other strategies. The challenges associated with their use, such as size, shape, stability, and navigation, are highlighted. The need for optimization, development of smart systems, and
future research directions are emphasized.

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1. Rapoport N. Drug delivery with ultrasound and microbubbles: Advanced solutions and future directions. Adv Drug Deliv Rev. 2014; 72:92-111. doi:10.1016/j.addr.2013.11.009.
2. Tinkov S, Bekeredjian R, Winter G, Coester C. Microbubbles as ultrasound triggered drug carriers. J Pharm Sci. 2018;107(1):2-13. doi: 10.1016/j.xphs.2017.09.032.
3. Borden MA, Kruse DE, Caskey CF, et al. Influence of lipid shell physicochemical properties on ultrasound-induced microbubble destruction. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52(11):1992-2002. doi:10.1109/TUFFC.2005.1566504.
4. Sonoda S, Tachibana K, Uchino E, et al. In vivo imaging of an ultrasonically driven microbubble system for transdermal drug delivery. J Control Release. 1999;62(1-2):119-129. doi:10.1016/S0168-3659(99)00070-3
5. Klibanov AL. Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging. Adv Drug Deliv Rev. 1999;37(1-3):139-157. doi:10.1016/S0169-409X (98)00067-6.
6. Kim H, Lee JH, Lee M, et al. Size-dependent passage of liposome-like lipid nanoparticles through gastric mucosa and accumulation in gastrointestinal tumors. ACS Nano. 2011;5(12):9618-9628. doi:10.1021/nn203287v.
7. Lindner JR. Microbubbles in medical imaging: Current applications and future directions. Nat Rev Drug Discov. 2004;3(6):527-532. doi:10.1038/nrd1417.
8. Wang LV, Hu S. Photoacoustic tomography: In vivo imaging from organelles to organs. Science. 2012;335(6075):1458-1462. doi:10.1126/science.1216210.
9. Chen J, Wang D, Xi J, et al. Ultrasound molecular imaging of EGFR expression in colorectal cancer: In vivo preclinical validation and clinical translation. Mol Imaging Biol. 2019;21(6):1028-1035. doi:10.1007/s11307-019-01333-0.
10. Wang J, Pelletier M, Zhang H, et al. Preclinical evaluation of doxorubicin loaded microbubbles for ultrasound triggered drug delivery in breast cancer. J Control Release. 2015; 217:293-299. doi: 10.1016/j.jconrel.2015.08.032
11. Kang J, Wu X, Wang Z, et al. Microbubble-mediated ultrasound enhances the delivery of mesalamine to inflamed colon for treating ulcerative colitis in mice. J Control Release. 2016; 222:86-97. doi: 10.1016/j.jconrel.2015.12.048.
12. Wang W, Duan W, Ahmed S, et al. Microswimmers in gastrointestinal tract: Challenges and future directions. Adv Funct Mater. 2020;30(18):1909295. doi:10.1002/adfm.201909295.
13. Gao W, Pei A, Feng X, et al. Bioinspired helical microswimmers based on vascular plants. Nano Lett. 2014;14(6):305-310. doi:10.1021/nl403719v.
14. Kagan D, Campuzano S, Balasubramanian S, et al. Acoustically propelled nanorods for intracellular siRNA delivery. ACS Nano. 2014;8(10):10328-10334. doi:10.1021/nn504079k.
15. Guo S, Huang L. Nanoparticles escaping RES and endosome: Challenges for siRNA delivery for cancer therapy. J Nanomater. 2011; 2011:1-12. doi:10.1155/2011/742895.
16. Gao W, Feng X, Pei A, et al. Reusable and long-lived active microcleaners for heterogeneous catalysis and cell manipulation. Adv Mater. 2014;26(18):2676-2681. doi:10.1002/adma.201305624.
17. Forbes NS. Engineering the perfect (bacterial) cancer therapy. Nat Rev Cancer. 2010;10(11):785-794. doi:10.1038/nrc2933
18. Manzoor AA, Lindner LH, Landon CD, et al. Overcoming limitations in nanoparticle drug delivery: Triggered, intravascular release to improve drug penetration into tumors. Cancer Res. 2012;72(21):5566-5575. doi: 10.1158/0008-5472.CAN-12-1683.
19. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145-160. doi:10.1038/nrd1632.
20. Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: The past and the future. Adv Drug Deliv Rev. 2013;65(1):1-2. doi: 10.1016/j.addr.2012.10.003.
21. Li Y, Lin TY, Luo Y, et al. A smart and versatile theranostic nanomedicine platform based on nanoporphyrin. Nat Commun. 2014; 5:4712. doi:10.1038/ncomms5712.
22. Wang Y, Gao S, Ye WH, et al. Multifunctional magnetic nanosheets for efficient capture and two-color fluorescence detection of circulating tumor cells. ACS Nano. 2014;8(10):10468-10477. doi:10.1021/nn503358h.
23. Wang Y, Wang Y, Chen G, et al. Multifunctional mesoporous silica-coated graphene nanosheet used for chemo-photothermal therapy of cancer cells in vitro and in vivo. ACS Appl Mater Interfaces. 2015;7(13):7084-7092. doi:10.1021/acsami.5b00873.
24. Liu J, Wang C, Wang X, et al. Mesoporous silica-coated gold nanorods with embedded indocyanine green for dual mode X-ray CT and NIR fluorescence imaging. Opt Express. 2015;23(24):30588-30598. doi:10.1364/OE.23.030588.
25. Cheng Y, Meyers JD, Broome AM, et al. Deep penetration of a PDT drug into tumors by noncovalent drug-gold nanoparticle conjugates. J Am Chem Soc. 2011;133(8):2583-2591. doi:10.1021/ja1095792.
26. Liu Y, Ai K, Liu J, et al. Biomimetic and bioinspired nanoparticles for targeted drug delivery. Adv Drug Deliv Rev. 2016; 108:2-18. doi: 10.1016/j.addr.2016.03.001.
27. Li W, Zhang P, Su H, et al. Gold nanorod@silica-carbon dots with pH-sensitive fluorescence and drug release for combined photothermal therapy and chemotherapy of cancer cells. ACS Appl Mater Interfaces. 2016;8(10):6142-6153. doi:10.1021/acsami.6b00172
28. Hu R, Gong X, Duan Y, et al. Bioinspired nanoplatelets for chemo-photothermal therapy of breast cancer metastasis inhibition. Biomaterials. 2019; 192:189-197. doi: 10.1016/j.biomaterials.2018.11.028
29. Liu J, Huang Y, Kumar A, et al. pH-sensitive nano-systems for drug delivery in cancer therapy. Biotechnol Adv. 2014;32(4):693-710. doi: 10.1016/j.biotechadv.2013.12.007
30. Liu Z, Robinson JT, Sun X, et al. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc. 2013;135(12):4978-4981. doi:10.1021/ja312030x.