An optimal drug delivery system should keep the drug load on the way to the target and release it only after

arrival at the target. Understanding the kinetics and mechanisms of drug release from liposomal (and other) nanocarriers is thus a prerequisite to systematically improving drug delivery systems. Acknowledgments The authers Inhibitors,research,lifescience,medical thank Drs. Alexander Wagner, Martin Holzer, and Rolf Schubert for illuminating discussions. S. May acknowledges support from NIH through Grant GM077184.
Protein-based therapeutics such as antibodies, blood derived products, and vaccines have been widely investigated in the past decade to treat a variety of disorders [1]. Development of a nanoparticulate-based dosage form of these molecules is still considered as a major challenge by scientists in the drug delivery field. Single emulsion (O/W), double emulsion (W/O/W), and

emulsion polymerization have been widely employed to prepare nanoparticles. Except emulsion polymerization, the other two methods (single and double emulsion) Inhibitors,research,lifescience,medical employ organic solvents and sonication during nanoparticle preparation. Protein-based therapeutics tend to exhibit rapid denaturation and conformational change due to sonication and exposure to organic solvents [2, 3]. These molecules may aggregate Inhibitors,research,lifescience,medical and eventually lose their biological activity due to selleck chemicals physical and chemical stress observed during formulation development, for example, exposure to organic solvents and sonication. These molecules may also denature or lose their biological activity during storage and lyophilization [4–6]. Sonication is employed to ensure homogeneous Inhibitors,research,lifescience,medical dispersion of

an emulsion. However, sonication may result in large pressure and temperature gradient which may cause denaturation and aggregation of the protein molecule [7]. Moreover, sonication also causes generation of high shear force and free radicals which cause protein denaturation [7]. Organic solvents preferentially interact with nonpolar amino acids Inhibitors,research,lifescience,medical of protein via hydrophobic interactions. Normally, these nonpolar amino acids are present in the core of the protein structure. As a result, in presence of organic solvents, the native structure and conformation of the protein can be altered. This process may result in loss of biological Sitaxentan activity of a protein molecule. Another crucial formulation-related limitation of protein molecules is their hydrophilicity. Due to their hydrophilic nature, these molecules often partition poorly into the polymeric matrix during encapsulation resulting in minimal loading in nanoparticles [1]. Due to poor loading of these molecules, a higher amount of polymer is needed to develop a formulation. Poly lactic-co-glycolic acid (PLGA) is one of the most widely employed biocompatible and biodegradable polymers utilized in the preparation of nanoparticles.