Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy.
In the present study, we used benchtop magnetic resonance imaging (BT-MRI) for non-invasive and continuous in vivo studies of in situ forming poly(lactide-co-glycolide) (PLGA) implants without the use of contrast agents. Polyethylene glycol (PEG) 400 was used as an alternative solvent to the clinically used NMP. In addition to BT-MRI, we applied electron paramagnetic resonance (EPR) spectroscopy to characterize implant formation and drug delivery processes in vitro and in vivo. We were able to follow key processes of implant formation by EPR and MRI. Because EPR spectra are sensitive to polarity and mobility, we were able to follow the kinetics of the solvent/non-solvent exchange and the PLGA precipitation. Due to the high water affinity of PEG 400, we observed a transient accumulation of water in the implant neighbourhood. Furthermore, we detected the encapsulation by BT-MRI of the implant as a response of the biological system to the polymer, followed by degradation over a period of two months. We could show that MRI in general has the potential to get new insights in the in vivo fate of in situ forming implants. The study also clearly shows that BT-MRI is a new viable and much less expensive alternative for superconducting MRI machines to monitor drug delivery processes in vivo in small mammals.
Kempe
Sabine
S
Martin-Luther-University Halle-Wittenberg, Department of Pharmaceutics and Biopharmaceutics, Halle/Saale, Germany.
Metz
Hendrik
H
Pereira
Priscila G C
PG
Mäder
Karsten
K
D000818:Animals; D011232:Chemical Precipitation; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D007279:Injections, Subcutaneous; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000191:economics / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011098:Polyglactin 910 / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D004343:Drug Implants; D012997:Solvents; D011098:Polyglactin 910; D011092:Polyethylene Glycols