Gelatin microparticles aggregates as three-dimensional scaffolding system in cartilage engineering

A three-dimensional (3D) scaffolding system for chondrocytes culture has been produced by agglomeration of cells and gelatin microparticles with a mild centrifuging process. The diameter of the microparticles, around 10 μ, was selected to be in the order of magnitude of the chondrocytes. No gel was used to stabilize the construct that maintained consistency just because of cell and extracellular matrix (ECM) adhesion to the substrate. In one series of samples the microparticles were charged with transforming growth factor, TGF-β1. The kinetics of growth factor delivery was assessed. The initial delivery was approximately 48 % of the total amount delivered up to day 14. Chondrocytes that had been previously expanded in monolayer culture, and thus dedifferentiated, adopted in this 3D environment a round morphology, both with presence or absence of growth factor delivery, with production of ECM that intermingles with gelatin particles. The pellet was stable from the first day of culture. Cell viability was assessed by MTS assay, showing higher absorption values in the cell/unloaded gelatin microparticle pellets than in cell pellets up to day 7. Nevertheless the absorption drops in the following culture times. On the contrary the cell viability of cell/TGF-β1 loaded gelatin microparticle pellets was constant during the 21 days of culture. The formation of actin stress fibres in the cytoskeleton and type I collagen expression was significantly reduced in both cell/gelatin microparticle pellets (with and without TGF-β1) with respect to cell pellet controls. Total type II collagen and sulphated glycosaminoglycans quantification show an enhancement of the production of ECM when TGF-β1 is delivered, as expected because this growth factor stimulate the chondrocyte proliferation and improve the functionality of the tissue.JLGR acknowledge the support of the Spanish Ministry of Education through project No. MAT2010-21611-C03-01 (including the FEDER financial support). The support of the Instituto de Salud Carlos III (ISCIII) through the CIBER initiative of the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) is also acknowledged

Generalization of a prototype intelligent hybrid system for hard gelatin capsule formulation development

The aim of this project was to expand a previously developed prototype expert network for use in the analysis of multiple biopharmaceutics classification system (BCS) class II drugs. The model drugs used were carbamazepine, chlorpropamide, diazepam, ibuprofen, ketoprofen, naproxen, and piroxicam. Recommended formulations were manufactured and tested for dissolution performance. A comprehensive training data set for the model drugs was developed and used to retrain the artificial neural network. The training and the system were validated based on the comparison of predicted and observed performance of the recommended formulations. The initial test of the system resulted in high error values, indicating poor prediction capabilities for drugs other than piroxicam. A new data set, containing 182 batches, was used for retraining. The percent of the test batches were used for cross-validation, resulting in models with R2≥70%. The comparison of observed performance to the predicted performance found that the system predicted succcessfully. The hybrid network was generally able to predict the amount of drug dissolved within 5% for the model drugs. Through validation, the system was proven to be capable of designing formulations that met specific drug performance criteria. By including parameters to address wettability and the intrinsic dissolution characteristics of the drugs, the hybrid system was shown to be suitable for analysis of multiple BCS class II drugs