Guy Draaisma

Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection

In this study, we investigated the potential of celecoxib-loaded polyester amide (PEA) microspheres as an auto-regulating drug delivery system for the treatment of pain associated with knee osteoarthritis (OA). Celecoxib release from PEA microspheres and inflammation responsive release of a small molecule from PEA was investigated in vitro. Inflammation responsive release of a small molecule from PEA was observed when PEA was exposed to cell lysates obtained from a neutrophil-like Hl-60 cell line. Following a short initial burst release of ~15% of the total drug load in the first days, celecoxib was slowly released throughout a period of >80days. To investigate biocompatibility and degradation behavior in vivo, celecoxib-loaded PEA microspheres were injected in OA-induced (ACLT+pMMx) or contralateral healthy knee joints of male Lewis rats. Bioactivity of celecoxib from loaded PEA microspheres was confirmed by PGE2 measurements in total rat knee homogenates. Intra-articular biocompatibility was demonstrated histologically, where no cartilage damage or synovial thickening and necrosis were observed after intra-articular injections with PEA microspheres. Degradation of PEA microspheres was significantly higher in OA induced knees compared to contralateral healthy knee joints, while loading the PEA microspheres with celecoxib significantly inhibited degradation, indicating a drug delivery system with auto regulatory behavior. In conclusion, this study suggests the potential of celecoxib-loaded PEA microspheres to be used as a safe drug delivery system with auto regulatory behavior for treatment of pain associated with OA of the knee.

Ligand exchange as a tool to improve quantum dot miscibility in polymer composite layers used as luminescent down-shifting layers for photovoltaic applications

The efficiency of solar cells with a poor UV response can be improved by altering the incident light spectrum with luminescence down-shifting (LDS). Stable luminescent additives with a large Stokes shift, high photoluminescence quantum yield (PLQY) and a high absorption coefficient are required for this purpose. Quantum dots (QDs) are attractive candidates which meet most of the basic requirements for LDS additives. Herein, commercially available heavy metal free core shell CuInS2/ZnS QDs are theoretically and experimentally evaluated as LDS additives. The small apolar dodecanethiol (DDT) ligands of the QDs are exchanged with thiol functional oligo-caprolactone ligands, via a ligand exchange process, to improve the QD compatibility with the UV curable resin matrix. Aggregation of the QDs is prevented to a large extent in the polymer–QD composite films and the material exhibits luminescence properties which are virtually identical to the luminescence of the QDs dispersed in chloroform. Raman spectroscopy and NMR spectroscopy are used to elucidate the ligand exchange and ligand binding processes. It is shown that well-dispersed CuInS2/ZnS QDs are required with a near unity quantum yield to increase the efficiency of solar cells significantly especially if high performance inorganic solar cells are employed.