Preparation and characterization of gelatin sponge millispheres injectable through microcatheters

Noboru Yamashita¹, Katsumi Saitou¹, Akira Takagi¹, Atsushi Maruyama²

¹Pharmaceutical Research and Technology Labs, Institute for Technology, Astellas Pharma Inc., 180 Ozumi, Yaizu-shi, Shizuoka-ken 425-0072, Japan; ²Institute for Materials Chemistry and Engineering, Kyushu University, 744-CE11 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

Objective: Millimeter size gelatin sponges are commonly used as an embolic agent for transcatheter arterial embolization (TAE). However the preparation of the fragments is troublesome and carries a risk of contamination. The purpose of this study was to develop gelatin sponge millispheres (GSMs), a convenient and reliable agent, and characterize them in vitro.

Method: The size of GSMs was controlled by modifying the previously reported method to include the use of caprylic triglyceride and isopropanol. Analytical and microbiological tests were conducted to detect impurities (caprylic triglyceride, isopropanol, endotoxins, bacteria, and fungus). The effects of syringe volume (1.0 to 5.0 ml) and contrast media viscosity (1.6 to 13.6 mPa * s) on the in vitro injectability of GSMs through microcatheters of various inner diameters (ID) (0. 43 to 0.53 mm) were examined via in-line pressure monitoring.

Results: The GSMs were found to be water-insoluble particles containing interconnected pores. The short and long diameters of the GSMs were 1.82 ± 0.2 mm and 2.37 ± 0.3 mm, respectively. The results of tests for impurities indicated that GSMs have the general properties necessary for medical devices. The GSMs were successfully injected without clogging through a microcatheter (ID: 0.53 mm) attached to a 1.0 or 2.5 ml syringe.

Conclusion: GSMs have the basic properties and injectability necessary to be considered reliable biomaterials (eg, embolic agents).

Keywords: embolic agents, gelatin sponge millispheres, injectable scaffolds, interconnected pores, microcatheter