Development of an in situ forming PLGA drug delivery system I. Characterization of a non-aqueous protein precipitation.
The incorporation of the model protein hen egg white lysozyme into liquid in situ forming poly(lactide-co-glycolide) (PLGA) implant or microparticle formulations was investigated. Ternary solvent blends of dimethyl sulfoxide (DMSO), ethyl acetate and water were used to adjust the protein solubility in order to facilitate the incorporation of either dispersed or dissolved protein into the polymer solution. Lysozyme formed large gel particles when dispersed directly in the polymer solution. These formulations had a pronounced initial release. Non-aqueous precipitation of lysozyme from solutions in DMSO with ethyl acetate led to a reversible aggregation without loss in biological activity. Lysozyme could be incorporated in a finely dispersed state through an in situ precipitation by non-solvent or polymer addition. Non-aqueous precipitation could thus be utilized to manufacture biodegradable in situ forming drug delivery systems containing homogeneously distributed and bioactive protein.
Körber
Martin
M
College of Pharmacy, Freie Universität Berlin, Germany. koerberm@zedat.fu-berlin.de
Bodmeier
Roland
R
D000085:Acetates; D002626:Chemistry, Pharmaceutical; D004121:Dimethyl Sulfoxide; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000737:chemistry*; D008837:Micrococcus / Q000187:drug effects; D009113:Muramidase / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D053758:Nanoparticles; D009391:Nephelometry and Turbidimetry; D010316:Particle Size; D017785:Photons; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011506:Proteins / Q000737:chemistry*; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013057:Spectrum Analysis; D014867:Water
D000085:Acetates; D011108:Polymers; D011506:Proteins; D012997:Solvents; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007650:ethyl acetate; D009113:Muramidase; D004121:Dimethyl Sulfoxide