Biodegradable nanocomposite microparticles as drug delivering injectable cell scaffolds

• Published in: Journal of controlled release 2011-11, Vol.156 (1), p.11-20
• Main Authors: Wen, Yanhong, Gallego, Monica Ramos, Nielsen, Lene Feldskov, Jorgensen, Lene, Everland, Hanne, Møller, Eva Horn, Nielsen, Hanne Mørck
• Format: Article
• Language: English
• Subjects: atomization; bioactive properties; biocompatibility; Biocompatible Materials - chemistry; biodegradability; Biodegradable materials; Biological and medical sciences; cell adhesion; Cell Adhesion - physiology; Chromatography, High Pressure Liquid; Composite scaffolds; Controlled drug delivery; crystal structure; Delayed-Action Preparations - administration & dosage; Drug Compounding; drugs; emulsions; fibroblasts; Fibroblasts - cytology; General pharmacology; Humans; Medical sciences; mPEG-PLGA microparticles; nanocomposites; nanoparticles; Nanoparticles - chemistry; Particle Size; Peptide Fragments - administration & dosage; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLA/PLGA nanoparticles; Polyesters - chemistry; Polyglactin 910 - chemistry; Solubility; stem cells; Stem Cells - cytology; Surface Properties; therapeutics; thrombin; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.07.013

Injectable cell scaffolds play a dual role in tissue engineering by supporting cellular functions and delivering bioactive molecules. The present study aimed at developing biodegradable nanocomposite microparticles with sustained drug delivery properties thus potentially being suitable for autologous stem cell therapy. Semi-crystalline poly( l-lactide/ dl-lactide) (PLDL70) and poly( l-lactide-co-glycolide) (PLGA85) were used to prepare nanoparticles by the double emulsion method. Uniform and spherical nanoparticles were obtained at an average size of 270–300 nm. The thrombin receptor activator peptide-6 (TRAP-6) was successfully loaded in PLDL70 and PLGA85 nanoparticles. During the 30 days' release, PLDL70 nanoparticles showed sustainable release with only 30% TRAP-6 released within the first 15 days, while almost 80% TRAP-6 was released from PLGA85 nanoparticles during the same time interval. The release mechanism was found to depend on the crystallinity and composition of the nanoparticles. Subsequently, mPEG-PLGA nanocomposite microparticles containing PLDL70 nanoparticles were produced by the ultrasonic atomization method and evaluated to successfully preserve the intrinsic particulate properties and the sustainable release profile, which was identical to that of the nanoparticles. Good cell adhesion of the human fibroblasts onto the nanocomposite microparticles was observed, indicating the desired cell biocompatibility. The presented results thus demonstrate the development of nanocomposite microparticles tailored for sustainable drug release for application as injectable cell scaffolds. PLA/PLGA-based nanocomposite microparticles as cell scaffolds for autologous stem cell therapy were designed with sustained drug release properties. [Display omitted]