Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

Sustained release Eudragit RL/RS microspheres encapsulating nifedipine were prepared using the acetone/liquid paraffin emulsion solvent evaporation method. The influence of different preparation factors on release of the drug in vitro was investigated. The release rate of nifedipine from the microspheres increased with increasing Eudragit RL/RS ratio and stirring rate during the preparation, and with decreasing the polymer concentration of internal phase and microsphere size. It was found that a linear relationship existed between the microsphere size and the time of 50% drug release. The drug release rate increased with increasing nifedipine content from 4.2 to 16.7% and was more rapid than the dissolution rate of pure nifedipine particles. However, the release rate of the microspheres with 26.6% drug content decreased significantly and was slower than the dissolution rate of pure drug particles. This was attributed mainly to the nifedipine dispersion state in the microspheres as confirmed by the differential thermal analysis and X ray diffraction study, which showed that nifedipine was present in an amorphous or molecular state in the microspheres with 4.2, 9.4 and 16.7% drug, whereas partly in the crystalline state in the microspheres with 26.6% drug. The amounts released for less than 70% nifedipine can be fitted to Higuchi square root of time model, independent of polymer ratio, drug content and microsphere size.

Preparation and Characterization of Lung-targeting Cefquinome-loaded PLGA Microspheres

We developed poly lactic-co-glycolic acid（PLGA） microspheres loaded with cefquinome and tested their effectiveness in a mouse model. The microspheres were prepared by optimizing several key parameters such as PLGA molecular weight, drug/polymer ratio, internal water volume and ethyl acetate. Drug loading efficiency, stability, in vitro release and tissue distribution in mouse were evaluated. The average particle size of the microspheres was 27.84 μm. The drug loading efficiency was 64.57%. The in vitro release of cefquinome from microspheres after 4 h was about 40% compared with over 90% for the drug alone. The concentration of cefquinome in lung reached 25 μg/g 0.25 h after injection, and kept at 10 μg/g 4 h after injection. However, the concentration of cefquinome was very low in other organs even 0.25 h after injection. In conclusion, Cefquinome-loaded PLGA microspheres are compatible as an effective lung-targeting drug delivery system and have a good sustained release efficacy.

Biodegradable chitosan scaffolds containing microspheres as carriers for controlled transforming growth factor-β_1 delivery for cartilage tissue engineering

Background Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-β1 （TGF-β1） to cartilage defects can enhance chondrogenesis. In this study, we assessed the feasibility of using biodegradable chitosan microspheres as carriers for controlled TGF-β1 delivery and the effect of released TGF-β1 on the chondrogenic potential of chondrocytes. Methods Chitosan scaffolds and chitosan microspheres loaded with TGF-β1 were prepared by the freeze-drying and the emulsion-crosslinking method respectively. In vitro drug release kinetics, as measured by enzyme-linked immunosorbent assay, was monitored for 7 days. Lysozyme degradation was performed for 4 weeks to detect in vitro degradability of the scaffolds and the microspheres. Rabbit chondrocytes were seeded on the scaffolds containing TGF-β1 microspheres and incubated in vitro for 3 weeks. Histological examination and type Ⅱ collagen immunohistochemical staining was performed to evaluate the effects of released TGF-β1 on cell adhesivity, proliferation and synthesis of the extracellular matrix. Results TGF-β1 was encapsulated into chitosan microspheres and the encapsulation efficiency of TGF-β1 was high （90.1%）. During 4 weeks of incubation in lysozyme solution for in vitro degradation, the mass of both the scaffolds and the microspheres decreased continuously and significant morphological changes was noticed. From the release experiments, it was found that TGF-β1 could be released from the microspheres in a multiphasic fashion including an initial burst phase, a slow linear release phase and a plateau phase. The release amount of TGF-β1 was 37.4%, 50.7%, 61.3%, and 63.5% for 1, 3, 5, and 7 days respectively. At 21 days after cultivation, type II collagen immunohistochemical staining was performed. The mean percentage of positive cells for collagen type II in control group （32.7%± 10.4%） was significantly lower than that in the controlled TGF-β1 release group （92.4%±4.8%, P〈0.05）. Both the proliferation rate and production of collagen type Ⅱ in the transforming growth factor-β1 microsphere incorporated scaffolds were significantly higher than those in the scaffolds without microspheres, indicating that the activity of TGF-β1 was retained during microsphere fabrication and after growth factor release. Conclusion Chitosan microspheres can serve as delivery vehicles for controlled release of TGF-β1, and the released growth factor can augment chondrocytes proliferation and synthesis of extracellular matrix. Chitosan scaffolds incorporated with chitosan microspheres loaded with TGF-β1 possess a promising potential to be applied for controlled cytokine delivery and cartilage tissue engineering.