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. 2024 Mar 11;7(1):27.
doi: 10.1186/s42155-024-00441-x.

In vitro study of the embolic characteristics of imipenem/cilastatin particles

Hiroki Nakamura  1 , Akira Yamamoto  2 , Takeshi Fukunaga  2 , Hiroyuki Watanabe  2 , Kosuke Ito  2 , Atushi Higaki  2 , Akihiko Kanki  2 , Yoshihiko Fukukura  2 , Tsutomu Tamada  2
Affiliations

In vitro study of the embolic characteristics of imipenem/cilastatin particles

Hiroki Nakamura et al. CVIR Endovasc. .

Abstract

Background: Imipenem/cilastatin (IPM/CS) has long been administered intravenously as a carbapenem antibiotic. However, since this agent is poorly soluble in liquid, occasional reports have described its use as a short-acting, temporary embolic agent. The purpose of this study was to elucidate the characteristics of IPM/CS particles, which are thought to have pain-relieving effects against osteoarthritis-related pain, as an embolic agent.

Methods: Three aspects of IPM/CS as an embolic agent were evaluated in vitro: particle size; particle shape; and change in particle size over time. For particle size, the long diameter was measured.

Results: Mean particle size (n=244) was 29.2±12.0 µm (range, 1-60 µm). Shape (n=109) was round in 18.35%, elliptical in 11.93%, and polygonal in 69.72%, showing that most particles were polygonal. In observations of changes in particle size over time (n=9), particles had decreased to 75% of their original size at 82±10.7 min, 50% at 89.3±9.14 min, 25% at 91.3±8.74 min, complete dissolved at 91.8±9.02 min. A rapid shrinkage in diameter was seen in the final period.

Conclusions: IPM/CS particles are ultrafine and the majority display a polygonal shape. This substance shows ultra-short embolic activity. This study revealed the characteristics of a substance that demonstrates an embolic effect not found in existing embolic materials.

Keywords: Electron microscopy; IPM/CS; Imipenem/cilastatin; Particle.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
a) Image of IPM/CS particles immediately after dissolution in contrast agent.(x20) b) The long diameter of each particle was measured using the microcell counter in BZ-X Analyzer, an analysis application. Particles suspected of polymerization in visual judgments were excluded.(x20) The particles being measured are displayed in red
Fig. 2
Fig. 2
Particle shape is classified as round (a), elliptical (b), or polygonal (c). A polygonal shape is one with three of more angles ≤90°, with any other shapes defined as either round or elliptical. An elliptical shape is taken as one with a short axis/long axis <0.75, and a round shape as one with a short axis/long axis ≥0.75. a Round (long axis/short axis = 0.92) (40×). b Elliptical (long axis/short axis = 0.58) (40×). c Polygonal (40×)
Fig. 3
Fig. 3
Distribution of long-axis lengths for IPM/CS particles
Fig. 4
Fig. 4
The shape is round in 18.35% of particles, elliptical in 11.93%, and polygonal in 69.72%. More than two-thirds present a polygonal shape
Fig. 5
Fig. 5
Changes over time until particle disappearance for the 9 observed particles under time-lapse imaging. a Immediately after dissolution (20×) The particles being measured are displayed in red. b After 20 min (20×). c After 40 min (20×). d After 60 min (20×). e After 80 min (20×). f After 100 min (20×)
Fig. 6
Fig. 6
Changes over time in long diameter of the 9 observed particles until disappearance
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