Biocompatibility of poly(D,L-lactic-co-hydroxymethyl glycolic acid) microspheres after subcutaneous and subcapsular renal injection
| Autor: | Kazazi-Hyseni, F., Zandstra, J., Popa, E. R., Goldschmeding, R., Lathuile, A. A R, Veldhuis, G. J., Van Nostrum, C. F., Hennink, W. E., Kok, R. J., Sub Drug delivery, Pharmaceutics |
|---|---|
| Přispěvatelé: | Sub Drug delivery, Pharmaceutics, Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Nanotechnology and Biophysics in Medicine (NANOBIOMED) |
| Rok vydání: | 2014 |
| Předmět: |
Male
Foreign-body giant cell Biocompatibility POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROCAPSULES Polyesters Monodisperse microspheres PLGA MICROSPHERES Pharmaceutical Science BIODEGRADATION Biocompatible Materials Administration Cutaneous Kidney INVIVO DEGRADATION PLHMGA Cell Line POLYMER DEGRADATION chemistry.chemical_compound Subcutaneous injection Drug Stability In vivo Taverne DELIVERY-SYSTEMS Polymer chemistry medicine Animals Glycolic acid Cell Proliferation Drug Carriers Chromatography Foreign-Body Reaction PROTEIN RELEASE IN-VITRO FUNCTIONALIZED POLY(ALPHA-HYDROXY ACID)S Cytocompatibility PARTICLE-SIZE Microspheres Rats PLGA medicine.anatomical_structure chemistry Drug carrier |
| Zdroj: | International Journal of Pharmaceutics, 482(1-2), 99. Elsevier bedrijfsinformatie b.v. International Journal of Pharmaceutics, 482(1-2), 99. Elsevier International Journal of Pharmaceutics, 482(1-2), 99-109. Elsevier Bedrijfsinformatie b.v. |
| ISSN: | 1873-3476 0378-5173 |
| Popis: | Poly(D,L-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) is a biodegradable copolymer with potential as a novel carrier in polymeric drug delivery systems. In this study, the biocompatibility of PLHMGA microspheres (PLHMGA-ms) was investigated both in vitro in three different cell types (PK-84, HK-2 and PTECs) and in vivo at two implantation sites (by subcutaneous and subcapsular renal injection) in rats. Both monodisperse (narrow size distribution) and polydisperse PLHMGA-ms were prepared with volume weight mean diameter of 34 and 17 mu m, respectively. Mono and polydisperse PLHMGA-ms showed good cytocompatibility properties upon 72 h incubation with the cells (100 mu g microspheres/600 mu L/cell line). A mild foreign body reaction was seen shortly after subcutaneous injection (20 mg per pocket) of both mono and polydisperse PLHMGA-ms with the presence of mainly macrophages, few foreign body giant cells and myofibroblasts. This transient inflammatory reaction diminished within 28 days after injection, the time-point at which the microspheres were degraded. The degradation profile is comparable to the in vitro degradation time of the microspheres (i.e., within 35 days) when incubated at 37 degrees C in phosphate buffered saline. Subcapsular renal injection of monodisperse PLHMGA-ms (10 mg) in rats was characterized with similar inflammatory patterns compared to the subcutaneous injection. No cortical damage was observed in the injected kidneys. In conclusion, this study demonstrates that PLHMGA-ms are well tolerated after in vivo injection in rats. This makes them a good candidate for controlled delivery systems of low-molecular weight drugs as well as protein biopharmaceuticals. (C) 2014 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect