Infrared microspectroscopy analysis of Ibuprofen release from drug eluting beads in uterine tissue J. Namur a, ⁎, M. Wassef b , J.P. Pelage c , A. Lewis d , M. Manfait a , A. Laurent e,f a MéDyC UMR CNRS 6237, unité MéDIAN, Université de Reims Champagne Ardennes, 51 rue Cognaq-Jay, 51096 Reims, France b Pathology Department, Lariboisière Hospital, 10 rue Ambroise, 75010 Paris, France c Radiology Department, Ambroise Paré Hospital, 9 avenue Charles de Gaulle, 92104 Boulogne-Billancourt, France d Biocompatibles UK, Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey, GU9 8QL, UK e Matière et Système Complexes, UMR CNRS 7057, Université Paris 7, 2 place Jussieu, 75006 Paris, France f Center for Research of Interventional Imaging (CR2i, AP/HP-INRA), Domaine de Vilvert, 78352 Jouy en Josas, France abstract article info Article history: Received 17 October 2008 Accepted 23 December 2008 Available online 19 January 2009 Keywords: Drug eluting beads Ibuprofen Embolization In vivo drug release Infrared microspectroscopy Ibuprofen loaded embolization beads (IBU-BB) have been developed to reduce inflammation and pain following uterine artery embolization for the treatment of uterine fibroids. The present work has investigated the elution properties of IBU-BB in situ after embolization with Fourier Transform Infrared Microspectroscopy (FTIRMS). Twelve sheep underwent uterine artery embolization with IBU-BB (485 mM) or control unloaded beads. IBU concentration was determined inside the beads and in the tissue surrounding the beads using FTIRMS of uterine tissue sections sampled 24 h or 1 week after embolization. After 24 h, IBU concentration inside the bead was only 18.6 mM out of the 485 mM initially loaded (p b 0.0001, univariate sign test). The concentration in the tissue around the beads was 8 mM, which is well above the in vitro therapeutic levels (6 μM). After one week the concentration of IBU had decreased to 4.9 mM in the beads (p =0.0502, Mann Whitney) and no IBU was detected in the surrounding tissue. This work has demonstrated that IBU-BB can provide a sustained release of the anti-inflammatory drug over at least one week. The in vivo elution properties of IBU-BB may be suitable to alleviate pain and inflammation after embolization. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Bead Block™ (BB) (Biocompatibles UK Ltd, Farnham, UK) is a polyvinyl alcohol based calibrated microsphere which has been FDA cleared for the embolization of hypervascular tumors such as uter- ine fibroid. To reduce the pain which is experienced by 92% of pa- tients after fibroid embolization [1], the loading of BB with the anti- inflammatory drug Ibuprofen (IBU-BB) has been proposed [2]. IBU-BB could potentially: 1) reduce the systemic and gastric exposure to the drug, hence reduce dose-related side effects (gastric erosion, thromb- asthenia or thrombocytopenia), 2) increase the local concentration of drug directly at the site of the lesion, and 3) provide a controlled delivery of IBU over an appropriate period of time. Two studies have partially demonstrated that IBU-BB have the above mentioned benefits [3,4]. Borovac et al. have demonstrated that a reduction of IBU plasma level is achieved after embolization with IBU- BB, when compared to a standard intra arterial administration. In addition, Borovac et al. showed in an in vitro model that IBU-BB provides a sustained release of the drug over a 24 h period [3]. Wassef et al. have noted that, in vivo, the release of IBU may extend to several days as supported by the significant decrease of inflammatory cells around IBU- BB one week after embolization in a sheep uterus model [4]. Two matters have not been inquired yet. First, the sustained release of IBU evidenced in vitro has to be thoroughly demonstrated in vivo after embolization, through the quantification of the drug still present within the microsphere at different time points. Secondly, it has to be proven that IBU-BB does deliver high levels of the drug to the tissue surrounding the microsphere. In order to quantify IBU both in the bead and in the surrounding tissue, we propose Fourier transform infrared microspectroscopy (FTIRMS). The technique is based on the coupling of a microscope with an IR spectrometer [5]. When a sample is irradiated with a beam of infrared light, peaks of absorbance, corresponding to the absorption of incident light by the molecules, appear at specific wavelengths characteristic for the sample. By coupling a microscope to the spectrometer, an IR image can be obtained and the drug distribution inside the sample can be visualized. FTIRMS has been already used to assess IBU concentration and repartition in drug formulations in vitro [6,7]. Vibrational microspectroscopies have also been successfully applied ex vivo to track different drugs in tissue specimen [8–10]. Journal of Controlled Release 135 (2009) 198–202 ⁎ Corresponding author. Tel.: +33 6 30 29 88 91; fax: +33 3 26 91 35 50. E-mail address: namurjul@hotmail.fr (J. Namur). 0168-3659/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2008.12.017 Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel