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Combined Application of Prototype Ultrasound and BSA-Loaded PLGA Particles for Protein Delivery

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A Correction to this article was published on 27 October 2021

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Abstract

Purpose

To develop an in vitro culture system for tissue engineering to mimic the in vivo environment and evaluate the applicability of ultrasound and PLGA particle system.

Methods

For tissue engineering, large molecules such as growth factors for cell differentiation should be supplied in a controlled manner into the culture system, and the in vivo microenvironment need to be reproduced in the system for the regulation of cellular function. In this study, portable prototype ultrasound with low intensity was devised and tested for protein release from bovine serum albumin (BSA)-loaded poly(lactic-co-glycolic acid) (PLGA) particles.

Results

BSA-loaded PLGA particles were prepared using various types of PLGA reagents and their physicochemical properties were characterized including particle size, shape, or aqueous wetting profiles. The BSA-loaded formulation showed nano-ranged size distribution with optimal physical stability during storage period, and protein release behaviors in a controlled manner. Notably, the application of prototype ultrasound with low intensity influenced protein release patterns in the culture system containing the BSA-loaded PLGA formulation. The results revealed that the portable ultrasound set controlled by the computer could contribute for the protein delivery in the culture medium.

Conclusions

This study suggests that combined application with ultrasound and protein-loaded PLGA encapsulation system could be utilized to improve culture system for tissue engineering or cell regeneration therapy.

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References

  1. Schroeder JE, Mosheiff R. Tissue engineering approaches for bone repair: concepts and evidence. Injury. 2011;42(6):609–13.

    Article  PubMed  Google Scholar 

  2. Wei J, Jia J, Wu F, Wei S, Zhou H, Zhang H, Shin J-W, Liu C. Hierarchically microporous/macroporous scaffold of magnesium–calcium phosphate for bone tissue regeneration. Biomaterials. 2010;31(6):1260–9.

    Article  CAS  PubMed  Google Scholar 

  3. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.

    Article  CAS  PubMed  Google Scholar 

  4. Liao H-T, Chen C-T. Osteogenic potential: comparison between bone marrow and adipose-derived mesenchymal stem cells. World journal of stem cells. 2014;6(3):288–95.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lindroos B, Suuronen R, Miettinen S. The potential of adipose stem cells in regenerative medicine. Stem Cell Rev Rep. 2011;7(2):269–91.

    Article  PubMed  Google Scholar 

  6. Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2012;64:61–71.

    Article  Google Scholar 

  7. Gombotz WR, Pettit DK. Biodegradable polymers for protein and peptide drug delivery. Bioconjug Chem. 1995;6(4):332–51.

    Article  CAS  PubMed  Google Scholar 

  8. Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3(3):1377–97.

    Article  CAS  PubMed  Google Scholar 

  9. Hu J, Ma PX. Nano-fibrous tissue engineering scaffolds capable of growth factor delivery. Pharm Res. 2011;28(6):1273–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Park SH, Park DS, Shin JW, Kang YG, Kim HK, Yoon TR, Shin J-W. Scaffolds for bone tissue engineering fabricated from two different materials by the rapid prototyping technique: PCL versus PLGA. J Mater Sci Mater Med. 2012;23(11):2671–8.

    Article  CAS  PubMed  Google Scholar 

  11. Tessmar JK, Göpferich AM. Matrices and scaffolds for protein delivery in tissue engineering. Adv Drug Deliv Rev. 2007;59(4–5):274–91.

    Article  CAS  PubMed  Google Scholar 

  12. Chen F-M, Zhang M, Wu Z-F. Toward delivery of multiple growth factors in tissue engineering. Biomaterials. 2010;31(24):6279–308.

    Article  CAS  PubMed  Google Scholar 

  13. Yilgor P, Tuzlakoglu K, Reis RL, Hasirci N, Hasirci V. Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. Biomaterials. 2009;30(21):3551–9.

    Article  CAS  PubMed  Google Scholar 

  14. Schmidmaier G, Wildemann B, Bail H, Lucke M, Fuchs T, Stemberger A, Flyvbjerg A, Haas N, Raschke M. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-β1) from a biodegradable poly (D, L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone. 2001;28(4):341–50.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang L, Gu F, Chan J, Wang A, Langer R, Farokhzad O. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol therapeutics. 2008;83(5):761–9.

    Article  CAS  Google Scholar 

  16. Gu W, Wu C, Chen J, Xiao Y. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration. Int J Nanomedicine. 2013;8:2305.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kim J-H, Kang MS, Eltohamy M, Kim T-H, Kim H-W. Dynamic mechanical and nanofibrous topological combinatory cues designed for periodontal ligament engineering. PLoS One. 2016;11(3):e0149967.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dey K, Roca E, Ramorino G, Sartore L. Progress in the mechanical modulation of cell functions in tissue engineering. Biomaterials Sci. 2020;8(24):7033–81.

    Article  CAS  Google Scholar 

  19. Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science. 2009;324(5935):1673–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vining KH, Mooney DJ. Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol. 2017;18(12):728–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gordon E, Schimmel L, Frye M. The importance of mechanical forces for in vitro endothelial cell biology. Front Physiol. 2020;11:684.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Burger E, Klein-Nulend J. Responses of bone cells to biomechanical forces in vitro. Adv Dent Res. 1999;13(1):93–8.

    Article  CAS  PubMed  Google Scholar 

  23. Mullender M, El Haj A, Yang Y, Van Duin M, Burger E, Klein-Nulend J. Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med Biol Eng Comput. 2004;42(1):14–21.

    Article  CAS  PubMed  Google Scholar 

  24. Clause KC, Liu LJ, Tobita K. Directed stem cell differentiation: the role of physical forces. Cell Commun Adhes. 2010;17(2):48–54.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wittkowske C, Reilly GC, Lacroix D, Perrault CM. In vitro bone cell models: impact of fluid shear stress on bone formation. Front Bioeng Biotechnol. 2016;4:87.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sun Y, Chen CS, Fu J. Forcing stem cells to behave: a biophysical perspective of the cellular microenvironment. Annu Rev Biophys. 2012;41:519–42.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Parker KJ, Doyley MM, Rubens DJ. Imaging the elastic properties of tissue: the 20 year perspective. Phys Med Biol. 2011;56(1):R1–R29.

    Article  CAS  PubMed  Google Scholar 

  28. Aliabouzar M. Lee Sj, Zhou X, Zhang GL, Sarkar K. effects of scaffold microstructure and low intensity pulsed ultrasound on chondrogenic differentiation of human mesenchymal stem cells. Biotechnol Bioeng. 2018;115(2):495–506.

    Article  CAS  PubMed  Google Scholar 

  29. Yang M-H, Lim K-T, Choung P-H, Cho C-S, Chung JH. Application of ultrasound stimulation in bone tissue engineering. Int J Stem Cells. 2010;3(2):74–9.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Moinnes JJ, Vidula N, Halim N, Othman SF. Ultrasound accelerated bone tissue engineering monitored with magnetic resonance microscopy. In.2006 International Conference of the IEEE Engineering in Medicine and Biology Society: IEEE; 2006. p. 484–488.

  31. Azuma Y, Ito M, Harada Y, Takagi H, Ohta T, Jingushi S. Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus. J Bone Miner Res. 2001;16(4):671–80.

    Article  CAS  PubMed  Google Scholar 

  32. Puts R, Ruschke K, Ambrosi TH, Kadow-Romacker A, Knaus P, Jenderka K-V, Raum K. A focused low-intensity pulsed ultrasound (FLIPUS) system for cell stimulation: physical and biological proof of principle. IEEE Trans Ultrason Ferroelectr Freq Control. 2015;63(1):91–100.

    Article  PubMed  Google Scholar 

  33. Feczkó T, Tóth J, Dósa G, Gyenis J. Optimization of protein encapsulation in PLGA nanoparticles. Chem Eng Process Process Intensif. 2011;50(8):757–65.

    Article  Google Scholar 

  34. Choi SA, Park EJ, Kim YH, Jee J-P, Kim S-T, Jang D-J, Min KA, Cho KH. Screening of electrolyte complexes formed between dextran sulfate and amine structures of small-molecule drugs. J Nanosci Nanotechnol. 2021;21(7):3679–82.

    Article  CAS  PubMed  Google Scholar 

  35. Kim D, Maharjan P, Jin M, Park T, Maharjan A, Amatya R, Yang J, Min KA, Shin MC. Potential Albumin-Based Antioxidant Nanoformulations for Ocular Protection against Oxidative Stress. Pharmaceutics. 2019;11:7.

    Article  Google Scholar 

  36. Maharjan P, Jin M, Kim D, Yang J, Maharjan A, Shin MC, Cho KH, Kim MS, Min KA. Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery. Arch Pharm Res. 2019;42(10):909–25.

    Article  CAS  PubMed  Google Scholar 

  37. Cochran MC, Eisenbrey J, Ouma RO, Soulen M, Wheatley MA. Doxorubicin and paclitaxel loaded microbubbles for ultrasound triggered drug delivery. Int J Pharm. 2011;414(1–2):161–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim JY, Kim DH, Min KA, Maeng H-J, Jang D-J, Cho KH. Preparation, characterization, and in vitro release of chitosan-Ecabet electrolyte complex for the mucosal delivery. J Nanosci Nanotechnol. 2019;19(2):640–5.

    Article  CAS  PubMed  Google Scholar 

  39. Khan I, Yousaf S, Najlah M, Ahmed W, Elhissi A. Proliposome powder or tablets for generating inhalable liposomes using a medical nebulizer. J Pharmaceutical Investig. 2021;51(1):61–73.

    Article  CAS  Google Scholar 

  40. Hooshyar S, Nafisi S, Mohseni M, Mehravi B. Design and synthesis of potential nano-carrier for delivery of diphencyprone to hair follicle. J Pharmaceutical Investig. 2021;51(2):173–81.

    Article  CAS  Google Scholar 

  41. Steinhilber D, Witting M, Zhang X, Staegemann M, Paulus F, Friess W, Küchler S, Haag R. Surfactant free preparation of biodegradable dendritic polyglycerol nanogels by inverse nanoprecipitation for encapsulation and release of pharmaceutical biomacromolecules. J Control Release. 2013;169(3):289–95.

    Article  CAS  PubMed  Google Scholar 

  42. Kim D, Amatya R, Hwang S, Lee S, Min KA, Shin MC. BSA-silver nanoparticles: a potential multimodal therapeutics for conventional and Photothermal treatment of skin Cancer. Pharmaceutics. 2021;13(4):575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Marhenke T, Sanabria SJ, Chintada BR, Furrer R, Neuenschwander J, Goksel O. Acoustic field characterization of medical array transducers based on unfocused transmits and single-plane hydrophone measurements. Sensors. 2019;19(4):863.

    Article  PubMed Central  Google Scholar 

  44. Yoon CW, Lee NS, Koo KM, Moon S, Goo K, Jung H, Yoon C, Lim HG, Shung KK. Investigation of ultrasound-mediated intracellular Ca2+ oscillations in HIT-T15 pancreatic β-cell line. Cells. 2020;9(5):1129.

    Article  CAS  PubMed Central  Google Scholar 

  45. Fukumoto A. The application of piezoelectric ceramics in diagnostic ultrasound transducers. Ferroelectrics. 1982;40(1):217–30.

    Article  CAS  Google Scholar 

  46. Tharkar P, Varanasi R, Wong WSF, Jin CT, Chrzanowski W. Nano-enhanced drug delivery and therapeutic ultrasound for cancer treatment and beyond. Front bioeng Biotechnol. 2019;7:324.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Erdoğar N, Akkın S, Nielsen TT, Özçelebi E, Erdoğdu B, Nemutlu E, İskit AB, Bilensoy E. Development of oral aprepitant-loaded chitosan–polyethylene glycol-coated cyclodextrin nanocapsules: formulation, characterization, and pharmacokinetic evaluation. J Pharmaceutical Investig. 2021;51:297–310.

    Article  Google Scholar 

  48. Xu J, Tu H, Ao Z, Chen Y, Danehy R, Guo F. Acoustic disruption of tumor endothelium and on-demand drug delivery for cancer chemotherapy. Nanotechnology. 2019;30(15):154001.

    Article  CAS  PubMed  Google Scholar 

  49. Murdoch AD, Grady LM, Ablett MP, Katopodi T, Meadows RS, Hardingham TE. Chondrogenic differentiation of human bone marrow stem cells in transwell cultures: generation of scaffold-free cartilage. Stem Cells. 2007;25(11):2786–96.

    Article  CAS  PubMed  Google Scholar 

  50. Li Y, Wu M, Zhang N, Tang C, Jiang P, Liu X, Yan F, Zheng H. Mechanisms of enhanced antiglioma efficacy of polysorbate 80-modified paclitaxel-loaded PLGA nanoparticles by focused ultrasound. J Cell Mol Med. 2018;22(9):4171–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Enayati M. Mohazey Da, Edirisinghe M, stride E. ultrasound-stimulated drug release from polymer micro and nanoparticles. Bioinspired, Biomimetic Nanobiomater. 2013;2(1):3–10.

    Article  CAS  Google Scholar 

  52. Sirsi SR, Borden MA. State-of-the-art materials for ultrasound-triggered drug delivery. Adv Drug Deliv Rev. 2014;72:3–14.

    Article  CAS  PubMed  Google Scholar 

  53. Shi X, Wang Y, Varshney RR, Ren L, Gong Y, Wang D-A. Microsphere-based drug releasing scaffolds for inducing osteogenesis of human mesenchymal stem cells in vitro. Eur J Pharm Sci. 2010;39(1–3):59–67.

    Article  CAS  PubMed  Google Scholar 

  54. Son JS, Kim SG, Oh JS, Appleford M, Oh S, Ong JL, Lee KB. Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration. J Biomed Mater Res A. 2011;99(4):638–47.

    Article  PubMed  Google Scholar 

  55. Hu Y, Zhang Y, Tian K, Xun C, Wang S, Lv D. Effects of nerve growth factor and basic fibroblast growth factor dual gene modification on rat bone marrow mesenchymal stem cell differentiation into neuron-like cells in vitro. Mol Med Rep. 2016;13(1):49–58.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Authors thank the staff in the public facility at Changwon National University for technical assistance on the instrumental analysis.

Funding

This work was supported by the 2017 Inje University research grant (no. 20180217).

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Correspondence to Changhan Yoon or Kyoung Ah Min.

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The original online version of this article was revised to update the affilations for Minki Jin and Sung Ho Seo.

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Jin, M., Seo, S.H., Kim, B.S. et al. Combined Application of Prototype Ultrasound and BSA-Loaded PLGA Particles for Protein Delivery. Pharm Res 38, 1455–1466 (2021). https://doi.org/10.1007/s11095-021-03091-z

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  • DOI: https://doi.org/10.1007/s11095-021-03091-z

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