title: Controlled protein delivery from electrospun non-wovens: novel combination of protein crystals and a biodegradable release matrix.
abstract: 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.
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg , Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Puhl
authors.forename: Linhao
authors.initials: L
authors.lastname: Li
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
authors.forename: Oliver
authors.initials: O
authors.lastname: Germershaus
mesh_terms: D002208:Caproates / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D009113:Muramidase / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013535:Suspensions / Q000737:chemistry
chemical_list: D002208:Caproates; D007783:Lactones; D011108:Polymers; D011506:Proteins; D012997:Solvents; D013535:Suspensions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C121056:caprolactone; D009113:Muramidase