Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep
| Autor: | Vera Luginbuehl, Bruno Gander, Lorenz Meinel, Brigitte von Rechenberg, Hans P. Merkle, Evangelos Zoidis |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Bone Regeneration medicine.medical_treatment Drug Compounding Polyesters Kinetics Pharmaceutical Science Bone healing Pharmacology Bone and Bones chemistry.chemical_compound Random Allocation Drug Delivery Systems Polylactic Acid-Polyglycolic Acid Copolymer Osteogenesis Cell Line Tumor Gene expression medicine Animals Humans Lactic Acid Insulin-Like Growth Factor I Growth Substances Sheep Domestic Bone growth Drug Implants Wound Healing Lactide Growth factor General Medicine In vitro Microspheres Recombinant Proteins Surgery PLGA chemistry Gene Expression Regulation Solubility Inflammation Mediators Polyglycolic Acid Biotechnology |
| Zdroj: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 85(1) |
| ISSN: | 1873-3441 |
| Popis: | Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly( d , l -lactide) (PLA) and poly( d , l -lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14–36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS ( n = 5) as compared to defects filled with IGF-I-free PL(G)A MS ( n = 4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies. |
| Databáze: | OpenAIRE |
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