Thursday, January 14, 2016

Article highlights use of PEG-PLGA for antibiotic delivery to bone as osteomyelitis treatment

PolySciTech division of Akina, Inc ( provides a wide array of biodegradable block copolymers including PEG-PLGA type polymers. These have the benefit of being easily formulated into microparticles by simple emulsion techniques (effectively rapidly stirring the organic solvent dissolved polymer into a water bath). One usefel aspect of these polymers is that the hydrophilic PEG-chain of the block copolymer naturally turns to the exterior of the microparticle upon emulsion. PEG has a very useful feature in that, due to its hydrodynamic structure, it is highly bio-inert and prevents protein absorption. This allows pegylated particles to resist immune system responses such as attack by macrophages and other forms of particle clearance that affect non-pegylated microparticles. In a recent study, a group for the University of Pavia in Italy generated a series of pegylated microparticles and investigated their application for delivery of gentamicin to bone structures to prevent postoperative orthopedic infections such as osteomyelitis. Read more: Dorati, Rossella, Antonella DeTrizio, Ida Genta, Pietro Grisoli, Alessia Merelli, Corrado Tomasi, and Bice Conti. "An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery." Materials Science and Engineering: C 58 (2016): 909-917.

“Abstract: The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1–97.5%), and span values of particle size distribution (1.03–1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone. Keywords: DOE; Gentamicin; Osteomyelitis; Microspheres; Polylactide-co-glycolide; Polyethyleneglycol; Bone delivery. Highlights: To get a more effective therapy for the prevention and treatment of osteomyelitis. To exploit the local delivery of gentamicin to bone by a biodegradable microparticulate drug delivery system. Polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microsphere as biodegradable drug delivery system. Process variables affecting microspheres properties are investigated. Design Of Experiment (DOE) screening design as approach to scale up manufacturing step.”

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