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Poly-ε-caprolactone (PCL) is an excellent polymer for electrospinning and matrix-controlled drug delivery combining optimal processability and good biocompatibility. Electrospinning of proteins has been shown to be challenging via the use of organic solvents, frequently resulting in protein unfolding or aggregation. Encapsulation of protein crystals represents an attractive but largely unexplored alternative to established protein encapsulation techniques because of increased thermodynamic stability and improved solvent resistance of the crystalline state. We herein explore the electrospinning of protein crystal suspensions and establish basic design principles for this novel type of protein delivery system. PCL was deployed as a matrix, and lysozyme was used as a crystallizing model protein. By rational combination of lysozyme crystals 0.7 or 2.1 μm in diameter and a PCL fiber diameter between 1.6 and 10 μm, release within the first 24 h could be varied between approximately 10 and 100%. Lysozyme loading of PCL microfibers between 0.5 and 5% was achieved without affecting processability. While relative release was unaffected by loading percentage, the amount of lysozyme released could be tailored. PCL was blended with poly(ethylene glycol) and poly(lactic-co-glycolic acid) to further modify the release rate. Under optimized conditions, an almost constant lysozyme release over 11 weeks was achieved.

Human African trypanosomiasis (HAT) or sleeping sickness is caused by two subspecies of Trypanosoma brucei , Trypanosoma brucei gambiense , and Trypanosoma brucei rhodesiense and is one of Africa's old plagues. It causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. Since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library was synthesized and tested. The biological evaluation illustrated that 4-quinolones with a benzylamide function in position 3 and cyclic or acyclic amines in position 7 exhibit high antitrypanosomal activity. Structure-activity relationships (SAR) are established to identify essential structural elements. This analysis led to lead structure 29, which exhibits promising in vitro activity against T. b. brucei (IC(50) = 47 nM) and T. b. rhodesiense (IC(50) = 9 nM) combined with low cytotoxicity against macrophages J774.1. Screening for morphological changes of trypanosomes treated with compounds 19 and 29 suggested differences in the morphology of mitochondria of treated cells compared to those of untreated cells. Segregation of the kinetoplast is hampered in trypanosomes treated with these compounds; however, topoisomerase II is probably not the main drug target.

The number of particulate delivery systems for biologics is negligible compared to liquid dosage forms, signifying the complications associated with development of solid protein delivery systems. Particulate protein delivery systems can improve stability, reduce viscosity of suspensions at high protein concentration and allow for controlled drug release. This review discusses current advances in controlled delivery of particulate protein formulations.While the focus lies on protein crystals and delivery systems employing protein crystals, amorphous protein particles will also be addressed. Crystallization and precipitations methods and modifications allowing controlled delivery with and without encapsulation are summarized and discussed.

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