| abstract |
A hydrophobic ion-pairing (HIP) complex is formed by the addition of an anionic surfactant, such as sodium dodecyl sulfate (SDS), to a polypeptide, protein, or other molecule in solution. Formation of an HIP complex alters the solubility and partitioning behavior of molecules. The HIP complex forms a precipitate which can be redissolved in an organic solvent to form a true homogeneous solution. The HIP complex partitions into an organic solvent at a rate of 2-4 orders of magnitude greater than that for uncomplexed material. The resulting protein maintains its structural and biological activity and exhibits a large increase in thermal stability. The HIP complex can be subsequently extracted back into an aqueous medium with retention of the native protein structure. Enzymes dissolved as an HIP complex can perform catalytic transformations in nonaqueous media. The homogeneous solution formed by the HIP complex in organic medium is useful in the formulation of a variety of systems to administer the drug to the body. The HIP complexation process can be controlled to yield in particles of a desired specific size. For example, for pulmonary delivery, proteins can be formulated into particles of 2-10 microns, within the particle size required for effective pulmonary delivery. |