Mikro-Kabarcığın Silika ile Kapsüllenerek Mukavemetinin Artırılması
Yıl 2024,
Cilt: 7 Sayı: 2, 80 - 87, 15.08.2024
Gizem Moğol
,
İbrahim Emre Gültaktı
,
Murat Akarsu
Öz
Geçmişten günümüze çeşitli tıbbi uygulamalarda kullanılmak üzere, vücut içinde etkin ve stabil kontrast ajanlarının geliştirilmesi için kapsamlı araştırmalar yapılmıştır. Özellikle tıbbi ultrason görüntüleme esnasında yüksek kontrast sağlayabilme yetenekleri ile dikkat çeken mikro-kabarcıklar (MBs), gaz çekirdeklerinin sıkıştırılması ve kanın ultrasonla etkileşimi sonucu deforme olarak, MBs’ nin kabuğundaki büzülme-genleşme hareketleri ile yaygın bir kontrast ajanı olarak kullanılmaktadır. MBs’ nin kabarcıkların çekirdek ve kapsül yapısı, kabarcığın stabilitesini ve bununla beraber etkinlik süresine etki etmektedir. Literatürdeki çalışmalar, farklı Q değerlerine sahip gaz çekirdek yapılı MBs’ nin lipit, protein, polimer ve sürfaktan gibi malzemelerle kapsüllendiğini göstermektedir. Bu kapsülasyon malzemeleri ile oluşturulan MBs’ nin ise tıbbi ultrasonik görüntülemede kullanılabilmesi için yeterli yapısal stabiliteye, etkin parçacık boyutuna ve yüksek kontrasta aynı anda sahip olması beklenmektedir. Bu araştırmada ise daha önce literatürde çalışılmamış olan n-pentan (C5) ve perfloropropan (C3H8) gazlarının sol-jel yöntemiyle silika (SiO2) kapsülasyonu yapılarak, 1-5 mikrometre arasında stabil MK elde edilmesi ve kontrast ajanı olarak kullanılması hedeflenmiştir. SiO2-C5 için en uygun sürfaktan miktarının ağırlıkça %10 olduğu belirlenmiş olup, amonyak katalizörünün artırılması ile ortalama hidrodinamik partikül boyutunun ise azaldığı gözlemlenmiştir. İdeal olarak belirlenen SiO2-C5 sistemleri, emülsiyon içinde 7 gün, hava ile etkileşiminde ise 10 dakika boyunca stabilitesini koruduğu görülmüştür. SiO2-C3H8 sistemleri için, çekirdek yapı miktarının arttırılması ile ortalama hidrodinamik parçacık boyutunun azaldığı, 15 güne kadar emülsiyon içinde, 15 dakika hava ile etkileşimi sonrasında stabilitesini koruduğu görülmüştür.
Etik Beyan
Çalışma tüm etik standartlara uygundur.
Destekleyen Kurum
Bu araştırmayı FYL-2021-5550 proje numarası ile destekleyen Akdeniz Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimine teşekkür ederiz.
Teşekkür
Akdeniz Üniversitesi personeline ve yönetimine bu çalışmadaki yardımları ve destekleri için içtenlikle teşekkür ederiz.
Kaynakça
- Meltzer R. S., Klig V., and Teichholz L.E., Generating precision microbubbles for use as an echocardiographic contrast agent, Journal of the American College of Cardiology, 1985. 5(4): p. 978-82. https://doi.org/10.1016/S0735-1097(85)80443-5
- Paul S., et al., Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery, Computational Mechanics., 2014. 53(3): p. 413–435. https://doi.org/10.1007/s00466-013-0962-4
- Rudakovskaya PG., et al., Microbubbles Stabilized by Protein Shell: From Pioneering Ultrasound Contrast Agents to Advanced Theranostic Systems, Pharmaceutics, 2022. 14(6): p.12-36. https://doi.org/10.3390/pharmaceutics14061236
- Holman,R. et al., Perfluorocarbon Emulsion Contrast Agents: A Mini Review, Frontiers in Chemistry. 2022. 9:810029. https://doi.org/10.3389/fchem.2021.810029
- Stride E., and Saffari N. Microbubble ultrasound contrast agents: a review. Proc Inst Mech Eng H. 2003. 217(6): p. 429-47. https://doi.org/10.1243/09544110360729072
- S. Unnikrishnan, and A. L. Klibanov, Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application, American journal of roentgenology, 2012. 199(2), p. 292-9. https://doi.org/10.2214/AJR.12.8826
- Butler, BD., Production of microbubbles for use as echo contrast agents, Journal of Clinical Ultrasound, 1986, 14(5): p. 408-412. https://doi.org/10.1002/jcu.1870140517
- Chowdhury, SM., Lee, T., and Willmann, JK, Ultrasound-guided drug delivery in cancer, Ultrasonography, 2017. 36(3): p. 171–184. https://doi.org/10.14366/usg.17021
- Burgess A., and Hynynen K, Microbubble-Assisted Ultrasound for Drug Delivery in the Brain and Central Nervous System. In: Escoffre JM, Bouakaz A, Editors. 2019, Therapeutic Ultrasound. Cham: Springer International Publishing, p. 293–308 https://doi.org/10.1007/978-3-319-22536-4_16
- Kabalnov, A., et al., Dissolution of multicomponent microbubbles in the bloodstream: 1. Theory, Ultrasound in Medicine & Biology, 1998. 24(5): p. 739-49. https://doi.org/10.1016/S0301-5629(98)00034-9
- Sirsi S., and Borden M., Microbubble compositions, properties and biomedical applications, Bubble science engineering and technology, 2009. 1(1-2): p. 3-17. https://doi.org/10.1179/175889709X446507
- Blomley, MJK., et al., Do different types of liver lesions differ in their uptake of the microbubble contrast agent SH U 508A in the late liver phase? Early experience, Radiology, 2001. 220(3): p. 661-7. https://doi.org/10.1148/radiol.2203992044
- Van, L.HD., and Raychaudhuri S., Stabilized bubbles in the body: pressure-radius relationships and the limits to stabilization, Journal of Applied Physiology, 1993. 82(6): p. 2045–2053. https://doi.org/10.1152/jappl.1997.82.6.2045
- Quay, S.C., Ultrasound contrastagents contaınıng mıcrobubbles of perfluoracarbon gasses. United States Patent Application Publication, 2004. Pub. No.:US 2004/0126321 A1.
- Jain A.K., Thareja S. In vitro and in vivo characterization of pharmaceutical nanocarriers used for drug delivery. Artif. Cells Nanomed. Biotechnol. 2019;47:524–539. https://doi.org/10.1080/21691401.2018.1561457
- Hamamoto S., Takemura T., Suzuki K., Nishimura T. Effects of pH on nano-bubble stability and transport in saturated porous media. J. Contam. Hydrol. 2018;208:61–67. https://doi.org/10.1016/j.jconhyd.2017.12.001
- Herth E., Zeggari R., Rauch JY., Remy-Martin F., Boireau W. Investigation of amorphous SiOx layer on gold surface for Surface Plasmon Resonance measurements. Microelectron. Eng. 163, C (September 2016), 43–48. https://doi.org/10.1016/j.mee.2016.04.014
- Chen BH, Liu JZ, Yuan JF, Zhou JH, Cen KF. Adsorption Behaviour of Tween 85 on Nano-Aluminium Particles in Aluminium/JP-10 Suspensions. J Nanosci Nanotechnol. 2019 Apr 1;19(4):2108-2115. https://doi.org/10.1166/jnn.2019.15803
- M. Jackson, H. Mantsch, Medical Science Applications of IR, Encyclopedia of Spectroscopy and Spectrometry (Second Edition) 1999, Pages 1494-1502. ISBN-10:0122266811, ISBN-13:978-0122266812
- A. B. Nandiyanto, R. Oktiani, R. Ragadhita, How to Read and Interpret FTIR Spectroscope of Organic Material, Indonesian Journal of Science & Technology ,07 Mar 2019-Vol. 4, Iss: 1, pp 97-118. https://doi.org/10.17509/ijost.v4i1.15806
- Park B, Yoon S, Choi Y, Jang J, Park S, Choi J. Stability of Engineered Micro or Nanobubbles for Biomedical Applications. Pharmaceutics. 2020 Nov 13;12(11):1089. https://doi.org/10.3390/pharmaceutics12111089
- Quay, Steven C. Edmonds, Use of selected perfluorocarbons for the preparation of diagnostic ultrasound contrast agents, European Patent Application, 27.09.2000, Pub. No. EP 1 038 535 A2
- Zeng D, Zhang H, Wang B, Sang K, Yang J. Effect of Ammonia Concentration on Silica Spheres Morphology and Solution Hydroxyl Concentration in Stober Process. J Nanosci Nanotechnol. 2015 Sep;15(9):7407-11. https://doi.org/10.1166/jnn.2015.10595
Increasing the Strength of the Micro-bubble by Encapsulating with Silica
Yıl 2024,
Cilt: 7 Sayı: 2, 80 - 87, 15.08.2024
Gizem Moğol
,
İbrahim Emre Gültaktı
,
Murat Akarsu
Öz
From the past to the present, comprehensive research has been conducted to develop effective and stable contrast agents within the body for various medical applications. Particularly, microbubbles (MBs) that exhibit high contrast capabilities during medical ultrasound imaging have garnered attention. These MBs deform when the gas core is compressed and when they interact with blood in the capillaries under ultrasound exposure. The deformation of MBs, characterized by the contraction-expansion movements of the MBs shell, has made them a widely used contrast agent. The core and shell structure of MBs significantly influence their stability and, consequently, their effectiveness. Studies in the literature have shown that MBs with gas cores having different Q values are encapsulated with materials such as lipids, proteins, polymers, and surfactants. These encapsulated MBs are expected to possess structural stability, effective particle size, and high contrast simultaneously to be suitable for medical ultrasound imaging. In this study, previously unexplored n-pentane (C5) and perfluoropropane (C3H8), were encapsulated within silica (SiO2) using the sol-gel method to obtain stable MBs ranging in size from 1 to 5 micrometers for use as contrast agents. It was determined that the optimal surfactant concentration for SiO2-C5 was 10% by weight and increasing the ammonia catalyst resulted in a decrease in the average hydrodynamic particle size. The SiO2-C5 systems, as ideally determined, maintained their stability for 7 days in emulsion and 10 minutes in contact with air. For the SiO2-C3H8 systems, it was observed that increasing the core structure amount resulted in a decrease in the average hydrodynamic particle size. These systems maintained their stability for up to 15 days in emulsion and 15 minutes when exposed to air.
Kaynakça
- Meltzer R. S., Klig V., and Teichholz L.E., Generating precision microbubbles for use as an echocardiographic contrast agent, Journal of the American College of Cardiology, 1985. 5(4): p. 978-82. https://doi.org/10.1016/S0735-1097(85)80443-5
- Paul S., et al., Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery, Computational Mechanics., 2014. 53(3): p. 413–435. https://doi.org/10.1007/s00466-013-0962-4
- Rudakovskaya PG., et al., Microbubbles Stabilized by Protein Shell: From Pioneering Ultrasound Contrast Agents to Advanced Theranostic Systems, Pharmaceutics, 2022. 14(6): p.12-36. https://doi.org/10.3390/pharmaceutics14061236
- Holman,R. et al., Perfluorocarbon Emulsion Contrast Agents: A Mini Review, Frontiers in Chemistry. 2022. 9:810029. https://doi.org/10.3389/fchem.2021.810029
- Stride E., and Saffari N. Microbubble ultrasound contrast agents: a review. Proc Inst Mech Eng H. 2003. 217(6): p. 429-47. https://doi.org/10.1243/09544110360729072
- S. Unnikrishnan, and A. L. Klibanov, Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application, American journal of roentgenology, 2012. 199(2), p. 292-9. https://doi.org/10.2214/AJR.12.8826
- Butler, BD., Production of microbubbles for use as echo contrast agents, Journal of Clinical Ultrasound, 1986, 14(5): p. 408-412. https://doi.org/10.1002/jcu.1870140517
- Chowdhury, SM., Lee, T., and Willmann, JK, Ultrasound-guided drug delivery in cancer, Ultrasonography, 2017. 36(3): p. 171–184. https://doi.org/10.14366/usg.17021
- Burgess A., and Hynynen K, Microbubble-Assisted Ultrasound for Drug Delivery in the Brain and Central Nervous System. In: Escoffre JM, Bouakaz A, Editors. 2019, Therapeutic Ultrasound. Cham: Springer International Publishing, p. 293–308 https://doi.org/10.1007/978-3-319-22536-4_16
- Kabalnov, A., et al., Dissolution of multicomponent microbubbles in the bloodstream: 1. Theory, Ultrasound in Medicine & Biology, 1998. 24(5): p. 739-49. https://doi.org/10.1016/S0301-5629(98)00034-9
- Sirsi S., and Borden M., Microbubble compositions, properties and biomedical applications, Bubble science engineering and technology, 2009. 1(1-2): p. 3-17. https://doi.org/10.1179/175889709X446507
- Blomley, MJK., et al., Do different types of liver lesions differ in their uptake of the microbubble contrast agent SH U 508A in the late liver phase? Early experience, Radiology, 2001. 220(3): p. 661-7. https://doi.org/10.1148/radiol.2203992044
- Van, L.HD., and Raychaudhuri S., Stabilized bubbles in the body: pressure-radius relationships and the limits to stabilization, Journal of Applied Physiology, 1993. 82(6): p. 2045–2053. https://doi.org/10.1152/jappl.1997.82.6.2045
- Quay, S.C., Ultrasound contrastagents contaınıng mıcrobubbles of perfluoracarbon gasses. United States Patent Application Publication, 2004. Pub. No.:US 2004/0126321 A1.
- Jain A.K., Thareja S. In vitro and in vivo characterization of pharmaceutical nanocarriers used for drug delivery. Artif. Cells Nanomed. Biotechnol. 2019;47:524–539. https://doi.org/10.1080/21691401.2018.1561457
- Hamamoto S., Takemura T., Suzuki K., Nishimura T. Effects of pH on nano-bubble stability and transport in saturated porous media. J. Contam. Hydrol. 2018;208:61–67. https://doi.org/10.1016/j.jconhyd.2017.12.001
- Herth E., Zeggari R., Rauch JY., Remy-Martin F., Boireau W. Investigation of amorphous SiOx layer on gold surface for Surface Plasmon Resonance measurements. Microelectron. Eng. 163, C (September 2016), 43–48. https://doi.org/10.1016/j.mee.2016.04.014
- Chen BH, Liu JZ, Yuan JF, Zhou JH, Cen KF. Adsorption Behaviour of Tween 85 on Nano-Aluminium Particles in Aluminium/JP-10 Suspensions. J Nanosci Nanotechnol. 2019 Apr 1;19(4):2108-2115. https://doi.org/10.1166/jnn.2019.15803
- M. Jackson, H. Mantsch, Medical Science Applications of IR, Encyclopedia of Spectroscopy and Spectrometry (Second Edition) 1999, Pages 1494-1502. ISBN-10:0122266811, ISBN-13:978-0122266812
- A. B. Nandiyanto, R. Oktiani, R. Ragadhita, How to Read and Interpret FTIR Spectroscope of Organic Material, Indonesian Journal of Science & Technology ,07 Mar 2019-Vol. 4, Iss: 1, pp 97-118. https://doi.org/10.17509/ijost.v4i1.15806
- Park B, Yoon S, Choi Y, Jang J, Park S, Choi J. Stability of Engineered Micro or Nanobubbles for Biomedical Applications. Pharmaceutics. 2020 Nov 13;12(11):1089. https://doi.org/10.3390/pharmaceutics12111089
- Quay, Steven C. Edmonds, Use of selected perfluorocarbons for the preparation of diagnostic ultrasound contrast agents, European Patent Application, 27.09.2000, Pub. No. EP 1 038 535 A2
- Zeng D, Zhang H, Wang B, Sang K, Yang J. Effect of Ammonia Concentration on Silica Spheres Morphology and Solution Hydroxyl Concentration in Stober Process. J Nanosci Nanotechnol. 2015 Sep;15(9):7407-11. https://doi.org/10.1166/jnn.2015.10595