کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1426995 986841 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
On the design of in situ forming biodegradable parenteral depot systems based on insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) nanoparticles
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
On the design of in situ forming biodegradable parenteral depot systems based on insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) nanoparticles
چکیده انگلیسی

The feasibility to generate in situ forming parenteral depot systems from insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) nanoparticles, was investigated. Biodegradable nanoparticles formed polymeric semi-solid depots upon injection into isotonic phosphate buffered saline (PBS) with no additional initiators. Nanoparticles (NP) prepared from the different amine-modified polyesters displayed a pronounced positive ζ-potential of > 25 mV. Diethylaminopropyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DEAPA(68)-PVAL-g-PLGA(1:20)), diethylaminoethyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DEAEA(33)-PVAL-g-PLGA(1:20)), and dimethylaminopropyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DMAPA(33)-PVAL-g-PLGA(1:20)), formed in situ depots by an ion-mediated aggregation with subsequent fusion of nanoparticles, related to a decreased glass transition temperature in the presence of PBS.Moreover, two factors, namely, polymer and insulin-nanocomplex concentration, were evaluated using a response surface design with respect to nanoparticles formation and insulin loading. Nanoparticles and implants were investigated by atomic force microscopy (AFM). The in vitro release from implants loaded with 2% insulin was carried out in a flow trough cell and quantified by high performance liquid chromatography (HPLC). The release showed a triphasic profile with an initial burst, pore diffusion and diffusion from the swollen matrix over more than two weeks. Insulin distribution in the implants during the release was followed by confocal laser scanning microscopy (CLSM). These findings combined with the protection of the model peptide against competitive macromolecules and the possibility to get dry powders by lyophilization make these nanoparticles-based depots suitable candidates for the design of controlled release devices for bioactive macromolecules.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 123, Issue 2, 6 November 2007, Pages 131–140
نویسندگان
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