Release and pharmacokinetics of near-infrared labeled albumin from monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcapsular renal injection

Release and pharmacokinetics of near-infrared labeled albumin from monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcapsular renal injection

[Display omitted] Subcapsular renal injection is a novel administration method for local delivery of therapeutics for the treatment of kidney related diseases. The aim of this study was to investigate the feasibility of polymeric microspheres for sustained release of protein therapeutics in the kidn...

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Bibliographic Details
Published in:Acta biomaterialia Vol. 22; pp. 141 - 154
Main Authors: Kazazi-Hyseni, F., van Vuuren, S.H., van der Giezen, D.M., Pieters, E.H., Ramazani, F., Rodriguez, S., Veldhuis, G.J., Goldschmeding, R., van Nostrum, C.F., Hennink, W.E., Kok, R.J.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-08-2015
Subjects:
Animals
Biomedical materials
Depot sustained release
Electrophoresis, Polyacrylamide Gel
Female
Fluorescence
Fluorescent Dyes - chemistry
Glycolic acid
In vitro–in vivo correlation
In vivo testing
In vivo tests
Infrared Rays
Injections
Kidney
Kidney - metabolism
Kidneys
Microspheres
Near-infrared imaging
Polyesters - chemistry
Proteins
Rats, Inbred F344
Serum Albumin, Bovine - administration & dosage
Serum Albumin, Bovine - pharmacokinetics
Staining and Labeling
Surgical implants
Tissue Distribution
Microspheres
Depot sustained release
Kidney
Near-infrared imaging
In vitro–in vivo correlation
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Summary:[Display omitted] Subcapsular renal injection is a novel administration method for local delivery of therapeutics for the treatment of kidney related diseases. The aim of this study was to investigate the feasibility of polymeric microspheres for sustained release of protein therapeutics in the kidney and study the subsequent redistribution of the released protein. For this purpose, monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres (40μm in diameter) loaded with near-infrared dye-labeled bovine serum albumin (NIR-BSA) were prepared by a membrane emulsification method. Rats were injected with either free NIR-BSA or with NIR-BSA loaded microspheres (NIR-BSA-ms) and the pharmacokinetics of the released NIR-BSA was studied for 3weeks by ex vivo imaging of organs and blood. Quantitative release data were obtained from kidney homogenates and possible metabolism of the protein was investigated by SDS–PAGE analysis of the samples. The ex vivo images showed a rapid decrease of the NIR signal within 24h in kidneys injected with free NIR-BSA, while, importantly, the signal of the labeled protein was still visible at day 21 in kidneys injected with NIR-BSA-ms. SDS–PAGE analysis of the kidney homogenates showed that intact NIR-BSA was released from the microspheres. The locally released NIR-BSA drained to the systemic circulation and subsequently accumulated in the liver, where it was degraded and excreted renally. The in vivo release of NIR-BSA was calculated after extracting the protein from the remaining microspheres in kidney homogenates. The in vivo release rate was faster (89±4% of the loading in 2weeks) compared to the in vitro release of NIR-BSA (38±1% in 2weeks). In conclusion, PLHMGA microspheres injected under the kidney capsule provide a local depot from which a formulated protein is released over a prolonged time-period.
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ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2015.04.030