• Ogris, Manfred
• Wagner, Ernst
• Schaffert, David
• Kasper, Julia Christina
• Friess, Wolfgang

Abstract

<p>Cationic polymer/DNA complexes are limited by their instability in aqueous suspensions and usually have to be freshly prepared prior to administration. Thus, the development of isotonic lyophilized polyplex formulations with long-term stability is a desirable goal.</p><p>Polyplexes based on 22 kDa linear polyethylenimine were prepared using a micro-mixer method. Freeze-thawing and lyophilization were performed on a pilot scale freeze-drier. Several excipients (trehalose, sucrose, lactosucrose, dextran, hydroxypropylbetadex or povidone and combinations thereof) at varying concentrations were evaluated for their stabilizing potential against freezing and dehydration induced stresses. For stability testing the lyophilized samples were stored for 6 weeks at 2-8 degrees C, 20 degrees C and 40 degrees C, respectively. Polyplex samples were characterized for particle size, zeta potential, their in vitro transfection efficiency and metabolic activity in Neuro2A cells. In addition, liquid samples were investigated for turbidity and number of sub-visible particles and solid samples were analyzed for residual moisture content, glass transition temperature and sample morphology.</p><p>L-histidine buffer pH 6.0 was selected as effective buffer. In isotonic formulations with 14% lactosucrose, 10% hydroxypropylbetadex/6.5% sucrose or 10% povidone/6.3% sucrose, particle size was 90 degrees C). (C) 2011 Published by Elsevier B.V.</p>

Topics

• impedance spectroscopy
• polymer
• glass
• glass
• glass transition temperature