Abstract
Purpose
To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility.
Materials and Methods
SAP-MS (HepaSphere150–200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR).
Results
The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5.
Conclusion
SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.
Graphical Abstract
Similar content being viewed by others
References
Nouri YM, Kim JH, Yoon H, Ko H, Shin JH, Gwon DI. Update on transarterial chemoembolization with drug-eluting microspheres for hepatocellular carcinoma. Korean J Radiol. 2019;20:34–49. https://doi.org/10.3348/kjr.2018.0088.
Bzeizi KI, Arabi M, Jamshidi N, Albenmousa A, Sanai FM, Al-Hamoudi W, et al. Conventional transarterial chemoembolization versus drug-eluting beads in patients with hepatocellular carcinoma: A systematic review and meta-analysis. Cancers (Basel). 2021;13:6172. https://doi.org/10.3390/cancers13246172.
Maeda N, Osuga K, Higashihara H, Mikami K, Tomoda K, Hori S, et al. In vitro characterization of cisplatin-loaded superabsorbent polymer microspheres designed for chemoembolization. J Vasc Interv Radiol. 2010;21:877–81. https://doi.org/10.1016/j.jvir.2010.02.009.
Jordan O, Denys A, De Baere T, Boulens N, Doelker E. Comparative study of chemoembolization loadable beads: in vitro drug release and physical properties of DC bead and hepasphere loaded with doxorubicin and irinotecan. J Vasc Interv Radiol. 2010;21:1084–90. https://doi.org/10.1016/j.jvir.2010.02.042.
Lee KH, Liapi EA, Cornell C, Reb P, Buijs M, Vossen JA, et al. Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer. Cardiovasc Intervent Radiol. 2010;33:576–82. https://doi.org/10.1007/s00270-010-9794-1.
Malagari K, Pomoni A, Filippiadis D, Kelekis D. Chemoembolization of hepatocellular carcinoma with HepaSphere. Hepat Oncol. 2015;2(2):147–57. https://doi.org/10.2217/hep.15.2.
Malagari K, Pomoni M, Moschouris H, Bouma E, Koskinas J, Stefaniotou A, et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc Intervent Radiol. 2012;35:1119–28. https://doi.org/10.1007/s00270-012-0394-0.
Malagari K, Moschouris H, Kiakidis T, Harward S, Kelekis A, Vrakas S, et al. Five-years outcome analysis of 142 consecutive hepatocellular carcinoma patients treated with doxorubicin eluting microspheres 30–60 mum: results from a single-centre prospective phase II trial. Cardiovasc Intervent Radiol. 2019;42:1551–62. https://doi.org/10.1007/s00270-019-02260-3.
Huppert P, Wenzel T, Wietholtz H. Transcatheter arterial chemoembolization (TACE) of colorectal cancer liver metastases by irinotecan-eluting microspheres in a salvage patient population. Cardiovasc Intervent Radiol. 2014;37:154–64. https://doi.org/10.1007/s00270-013-0632-0.
Seki A, Hori S, Kobayashi K, Narumiya S. Transcatheter arterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres for 135 hepatocellular carcinoma patients: single-center experience. Cardiovasc Intervent Radiol. 2011;34:557–65. https://doi.org/10.1007/s00270-010-9975-y.
Seki A, Hori S. Switching the loaded agent from epirubicin to cisplatin: salvage transcatheter arterial chemoembolization with drug-eluting microspheres for unresectable hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2012;35(3):555–62. Epub 20110512. https://doi.org/10.1007/s00270-011-0176-0
Namur J, Wassef M, Pelage JP, Lewis A, Manfait M, Laurent A. Infrared microspectroscopy analysis of ibuprofen release from drug eluting beads in uterine tissue. J Control Release. 2009;135:198–202. https://doi.org/10.1016/j.jconrel.2008.12.017.
Bedouet L, Moine L, Servais E, Beilvert A, Labarre D, Laurent A. Tunable delivery of niflumic acid from resorbable embolization microspheres for uterine fibroid embolization. Int J Pharm. 2016;511:253–61. https://doi.org/10.1016/j.ijpharm.2016.06.128.
Tian C, Wang Z, Huang L, Liu Y, Wu K, Li Z, et al. One-step fabrication of lidocaine/CalliSpheres((R)) composites for painless transcatheter arterial embolization. J Transl Med. 2022;20:463–8. https://doi.org/10.1186/s12967-022-03653-8.
Jiaqi Y, Hori S, Minamitani K, Hashimoto T, Yoshimura H, Nomura N, et al. A new embolic material: super absorbent polymer (SAP) microsphere and its embolic effects. Nippon Igaku Hoshasen Gakkai Zasshi. 1996;56:19–24.
Narita A, Yamamoto T, Ikeda S, Izumi Y, Kitagawa A, Takeda M, et al. In vitro evaluation of radiopacity of contrast-loaded superabsorbent polymer microspheres (SAP-MS) with static imaging and flow model. Jpn J Radiol. 2019;37:710–8. https://doi.org/10.1007/s11604-019-00863-x.
Han K, Kim SY, Kim HJ, Kwon JH, Kim GM, Lee J, et al. Nonspherical Polyvinyl alcohol particles versus tris-acryl microspheres: randomized controlled trial comparing pain after uterine artery embolization for symptomatic fibroids. Radiology. 2021;298:458–65. https://doi.org/10.1148/radiol.2020201895.
Lohle PNM, De Vries J, Klazen CAH, Boekkooi PF, Vervest HAM, Smeets AJ, et al. Uterine artery embolization for symptomatic adenomyosis with or without uterine leiomyomas with the use of calibrated tris-acryl gelatin microspheres: midterm clinical and MR imaging follow-up. J Vasc Interv Radiol. 2007;18:835–41. https://doi.org/10.1016/j.jvir.2007.04.024.
Noel-Lamy M, Tan KT, Simons ME, Sniderman KW, Mironov O, Rajan DK, et al. Intraarterial lidocaine for pain control in uterine artery embolization: a prospective. Randomized Study J Vasc Interv Radiol. 2017;28:16–22. https://doi.org/10.1016/j.jvir.2016.10.001.
Liu S, Li W. Intra-arterial lidocaine for pain control after uterine artery embolization: a meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2022;35:4162–7. https://doi.org/10.1080/14767058.2020.1847079.
Alqahtani A, Han K, Kim SY, Kim M, Kwon JH, Kim GM, et al. Efficacy of intra-arterial lidocaine administration on pain and inflammatory response after uterine artery embolization for symptomatic fibroids. Acta Radiol. 2023:2841851221146517. https://doi.org/10.1177/02841851221146517
Zaitoun MMA, Basha MAA, Elsayed SB, El Deen DS, Zaitoun NA, Alturkistani H, et al. Comparison of three embolic materials at partial splenic artery embolization for hypersplenism: clinical, laboratory, and radiological outcomes. Insights Imaging. 2021;12:85–95. https://doi.org/10.1186/s13244-021-01030-5.
Masada T, Tanaka T, Sakaguchi H, Nakagomi M, Miura Y, Hidaka T, et al. Coils versus gelatin particles with or without intraarterial antibiotics for partial splenic embolization: a comparative evaluation. J Vasc Interv Radiol. 2014;25:852–8. https://doi.org/10.1016/j.jvir.2013.12.563.
Bundy JJ, Hage AN, Srinivasa RN, Gemmete JJ, Srinivasa RN, Jairath N, et al. Intra-arterial ampicillin and gentamicin and the incidence of splenic abscesses following splenic artery embolization: A 20-year case control study. Clin Imaging. 2019;54:6–11. https://doi.org/10.1016/j.clinimag.2018.10.005.
Gupta AK, Nelson RC, Johnson GA, Paulson EK, Delong DM, Yoshizumi TT. Optimization of eight-element multi-detector row helical CT technology for evaluation of the abdomen. Radiology. 2003;227:739–45. https://doi.org/10.1148/radiol.2273020591.
Flum AS, Hamoui N, Said MA, Yang XJ, Casalino DD, McGuire BB, et al. Update on the diagnosis and management of renal angiomyolipoma. J Urol. 2016;195:834–46. https://doi.org/10.1016/j.juro.2015.07.126.
Osuga K, Hori S, Kitayoshi H, Khankan AA, Okada A, Sugiura T, et al. Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres. J Vasc Interv Radiol. 2002;13:1125–33. https://doi.org/10.1016/s1051-0443(07)61954-x.
Bonomo G, Pedicini V, Monfardini L, Della Vigna P, Poretti D, Orgera G, et al. Bland embolization in patients with unresectable hepatocellular carcinoma using precise, tightly size-calibrated, anti-inflammatory microparticles: first clinical experience and one-year follow-up. Cardiovasc Intervent Radiol. 2010;33:552–9. https://doi.org/10.1007/s00270-009-9752-y.
Brown KT. Fatal pulmonary complications after arterial embolization with 40–120-micro m tris-acryl gelatin microspheres. J Vasc Interv Radiol. 2004;15:197–200. https://doi.org/10.1097/01.rvi.0000109400.52762.1f.
Chehab MA, Thakor AS, Tulin-Silver S, Connolly BL, Cahill AM, Ward TJ, et al. Adult and pediatric antibiotic prophylaxis during vascular and ir procedures: a society of interventional radiology practice parameter update endorsed by the cardiovascular and interventional radiological society of europe and the canadian association for interventional radiology. J Vasc Interv Radiol. 2018;29:1483–501. https://doi.org/10.1016/j.jvir.2018.06.007.
Flory PJ, CHAPTER XIII. Phase equilibria in polymer systems. Principles of Polymer Chemistry. 1st ed. Ithaca, NY: Cornell University Press; 1953.
Capoor MN, Lochman J, McDowell A, Schmitz JE, Solansky M, Zapletalova M, et al. (2019) Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections. Eur Spine J. 2019;28:783–91. https://doi.org/10.1007/s00586-018-5838-z.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Number JP20K16806. We thank Natsumi Kodama (Aichi Medical University, institute of comprehensive medical research, division of advanced research promotion) for the assistance in reverse-phase high-performance liquid chromatography analyses.
Funding
This study was funded by JSPS KAKENHI (Grant Number JP20K16806).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed Consent
For this type of study informed consent is not required.
Consent for Publication
For this type of study consent for publication is not required.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Narita, A., Nakano, Y., Okada, H. et al. In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics. Cardiovasc Intervent Radiol 46, 1632–1640 (2023). https://doi.org/10.1007/s00270-023-03559-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00270-023-03559-y