• Araujo Filho, W. D. State University Of Bahia (UNEB) - Collegiate Of Physics-Department Of Exact And Earth Sci-ences (DCET 1) - Micro Fluidic Laboratory (LAMIC), Brazil
  • Chaves Antônio, A. G. S State University of Bahia (UNEB) - Collegiate of Physics-Department of Exact and Earth Sciences (DCET 1) - Micro Fluidic Laboratory (LAMIC)
  • dos Santos, F. F. State University of Bahia (UNEB) - Department of Life Sciences (DCV), Laboratory of Biopharmacy and Drug Analysis
  • Santos Junior, A. F. State University of Bahia (UNEB) - Department of Life Sciences (DCV), Laboratory of Biopharmacy and Drug Analysis



Microbubbles, Ultrasound, Drugs, Tumours Tratment

Abstract [English]

INTRODUCTION: The localized delivery of drugs has been established since the early eighties of the 20th century as a promising alternative for the localized treatment of tumours, based on the mitigation of side effects produced by traditional methods, notably the administration of chemotherapy by systemic route. Countless scientific works have been dealing with this theme in an attempt to make this therapeutic technique viable and accessible. One of the ways to take the drug to the chosen site is through the use of microbubbles as drug carrier units activated through an ultrasonic field with adequate wavelength and frequency. Therefore, these units must have very peculiar characteristics, such as dimensions, homogeneity, echogenicity and structural characteristics, in addition to the ability to take the therapeutic vector intact to the desired location. In the generation of microbubbles, microfluidic devices of different geometries and different configurations are used, according to the state of the art related to this theme. DEVELOPMENT: In this work the technique used is the fabrication of micro fluidic devices using 3D printing. With this technique, it is possible to manufacture the devices in a single step, eliminating time-consuming and more complex intermediate procedures. The devices were manufactured using an Object Eden 250 printer, using the transparent resin VeroClear®. With these devices it was possible to produce microbubbles with diameters of the order of 16-73 µm with degrees of poly dispersion less than 1%. However, there are difficulties to be overcome, notably with regard to the final composition of the devices. Due to the physical characteristics of the microbubble, notably in relation to its lipid coating layer, the search for drug transport systems is an important strategy.  CONCLUSION: In this work, an account of these difficulties will be made, in addition to the proposition of alternatives to overcome them. Additionally, compatible drugs will be suggested to be attached to microbubbles according to their structural composition.


Download data is not yet available.


Abolmaali, S. S., Tamaddon, A. M., Dinarvand, R. 2013. "A review of therapeutic challenges and achievements of methotrexate delivery systems for treatment of cancer and rheumatoid arthritis". Cancer Chemotherapy Pharmacololy. 71:1115-1130. Retrived from DOI:

Allen, M. T., Cullis, R. P. 2012. "Liposomal drug delivery systems: From concept to clinical applications". Advanced Drug Delivery Reviews, 65:36-48. Retrived from DOI:

Araujo Filho, W. D. et al. "Evaluation of stability and size distribution of sunflower oil coated micro bubbles for localized drug delivery. Biomedical Engineering OnLine,11:71. Retrived from DOI:

Araujo Filho, W. D.; Araujo, L. M.P. Monodisperse Microbubbles as Drug Carrier Units Having the Olive Oil as the Coating Layer from Devices Manufactured by 3D Printing. International Journal of Biosensors & Bioelectronics, v. 3, p.00059-00064, 2017. Retrived from DOI:

Araujo Filho, W. D.; Araujo, L. M.P.; Menezes, D. O.; Mauricio, C. R. M. 2019 3D Printing Techniques in the Manufacture of Microfluidic Devices for Generation of Microbubbles. SCIOL Biomedicine, v. 3, p. 143,.

Araujo Filho, W. D.; Araujo, L. M.P.; Menezes, D. O.; Mauricio, C. R. M. Annexation of Biologically active compounds extracted from plants in the lipid layers of microbubbles for the localized treatment of diseases. DISEASES.INTERNATIONAL JOURNAL OF CURRENT RESEARCH, v. 10, p. 72208-72211, 2018.

Barrat, G. M. 2000. "Therapeutic applications of colloidal drug carriers". Pharma. Sci. Technol. 5:163-171. Retrived from DOI:

Bizerra, A., Silva, V. 2016. "Sistema de Liberação controlada. Revista de Saúde e Meio ambiente". Mato Grosso. 3(2):1-12.

Borden, M. A., M. L. Longo. 2002. "Dissolution behaviour of lipid monolayer coated, air-filled micro bubbles: Effect of lipid hydophobic chain length". Langmuir. 18(24):9225-9233. Retrived from DOI:

E stride, M Edirisinghe 2008. Novel microbubble preparation technologies. soft Matter; 4:2350. Retrived from DOI:

EC Unger, T Porter, W Culp, R label, T Matsunaga, R Zutshi 2004. Therapeutic applications of lipid-coated microbubbles. adv Drug Deliv Rev; 56:1291-314. Retrived from DOI:

Ferguson, H. M., Fréchet, J., Szoka, F. C. 2013. "Clinical developments of chemotherapeutic nanomedicines: polymers and liposomes for delivery of camptothecins and platinum (II) drugs". WIREs Nanomedicine and Nanobiotechnology. 5(2):130-138. Retrived from DOI:

Fillippin, B. F., Souza, C. L. 2006. "Eficiência terapêutica das formulações lipídicas de anfotericina B". Revista Brasileira de Ciências Farmacêuticas. 42:167-194. Retrived from DOI:

Fiorini, D. T. Chiu 2005. Disposable microfluidic devices: Fabrication, function, and application. Bio techniques; 38:429-46. Retrived from DOI:

Gaies, E., Jebabli, N., Trabelsi, S., Salouage, I., Charfi, R., Lakhal, M., Klouz, A. 2012. "Methotrexate Side Effects: Review Article". Drug Metabolism & Toxicology. 3(4):1-5. Retrived from DOI:

Garstecki, P. 2010. "Formation of Droplets and Bubbles in Microfluidic Systems". Microfluidics Based Microsystems: Fundamentals and Applications". 163-181. Retrived from DOI:

Gref, R., Minamitake, Y., Peracchia, M. T., Trubetskoy, V., Torchilin, V., Langer, R. 1994. "Biodegradable long-circulating polymeric nanospheres". Science. 263:1600-1603. Retrived from DOI:

Huang, X., Li, Z., Yu, Z., Deng, X., Yi, X. 2019. "Recent Advances in the Synthesis, Properties, and Biological Applications of Platinum Nanoclusters". Journal of Nanomaterials. 2019:6248725. Retrived from DOI:

Lajoline, G. et al. 2016. In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications. Bio microfluidics, v. 10, n. 1, p. 011501. Retrived from DOI:

Levêque, D., Santucci, R., Gourieux, B., Herbrecht, R. 2011. "Pharmacokinetic drug-drug interactions with methotrexate in oncology". Expert Review of Clinical Pharmacology. 4(6):743-750. Retrived from DOI:

Lindner, J. R., S. Kaul. 2001. "Delivery of drugs with ultrasound Echocardiography." 18(4): 329-337. 2001. Retrived from DOI:

Neves, A. P., Vargas, M. D. 2011. "Complexo de Platina (II) na Terapia do Câncer". Revista Virtual de Quimica. 3:196-209. Retrived from DOI:

P Garstecki, I Gitlin, W Diluzio, GM Whitesides, E Kumacheva, 2004 Ha stone . Formation of monodisperse bubbles in a microfluidic flow-focusing device. appl Phys lett; 85:2649-51. Retrived from DOI:

Pancholi, K., E. Stride, et al. 2008. "Generation of microbubbles for diagnostic and therapeutic applications using a novel device. "J Drug Target., 16(6): 494-501. DOI:

Pontes, A. C., Caetano, M. N., Magalhaes, N. S. 1999. "Physicochemical characterization and antimicrobial activity of benzathine penicillin G liposomes". S. T. P. Pharma Sci. 9:419-427.

Puig, L. 2014. "Methotrexate: New Therapeutic Approaches". Actas Dermosifiliogr. 6:583-589. Retrived from DOI:

Schaffazick, R. S., Guterres, S. S. 2003. "Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos". Qumica Nova. 26(5):726-737. Retrived from DOI:

Sharma, P., Mukherjee, A., Karunanithi, S., Bal, C., Kumar, R. 2014. "Potencial role of ISF-FDG, PET/CT in patients with fungal infection". Am. J. Roentgenol. 203:180-189. Retrived from DOI:

Shen, S., Kuznetsov, I., Abakumova, T., Chelushkin, P., Melnikov, P., Korchagina, A., Bychkov, D., Seregina, F., Bolshov, M., Kabanov, A., Chekhonin, V., Nukolova, N. 2016. "VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells". Mol. Pharmaceutics. 13:3712-3723. Retrived from DOI:

Sorbello, G. S., Bertino, J. R. 2001. "Current understanding of methotrexate pharmacology and efficacy in acute leukemias. Use of newer antifolates in clinical trials". Haematologica. 86(2):121-127. Retrived from

Stride, E. 2009. "Physical principles of micro bubbles for ultrasound imaging and therapy. "cerebrovascular Dis 27 Suppl, 2: 1-13. Retrived from

Stride, E. 2009. "Physical principles of micro bubbles for ultrasound imaging and therapy. "cerebrovascular Dis 27 Supply, 2: 1-13. Retrived from DOI:

Stride, E., M. Edrisinghe. 2009. "Novel preparation techniques for controlling micro bubble uniformity: a comparison. "Med Biol Eng Comput., 47(8): 883-892. Retrived from DOI:

T Fu, Y Ma, D Fun schilling, HZ li 2009. Bubble formation and breakup mechanism in a microfluidic flow-focusing device. Chem Eng sci; 64:2392-400. Retrived from DOI:

TM Squires, SR Quake 2005. Microfluidics: Fluid physics at the nanoliter scale. Rev Mod Phys; 77:977-1026. Retrived from DOI:

Y Hong, F Wang 2007. Flow rate effect on droplet control in a co-flowing microfluidic device. Micro fluid Nano fluidics; 3:341-6. Retrived from DOI:




How to Cite