Physicochemical studies of carrier systems for peptide drug delivery

Polystyrene and dextran microspheres were investigated as model carriers for small molecular weight peptide drug delivery systems.;Polystyrene was characterized by particle sizing, atomic force microscopy (AFM), surface area measurements, and surface charge density. AFM topographical images of polystyrene depicted a highly irregular surface with crater-like depressions (d ;The adsorption and desorption characteristics of lysine vasopressin, a model nonapeptide, at polystyrene surfaces were studied as functions of pH, ionic strength, dilution volume, and surface tension. Adsorption occurred by hydrophobic and electrostatic interactions and was greatest in the region of the isoelectric point. Although no single parameter provided complete desorption, partial desorption occurred at pH values away from the isoelectric point, at low ionic strengths, and at low surface tensions. AFM images of polystyrene in the presence of lysine vasopressin showed surface irregularities which were quite different from those of the polystyrene surface itself.;Initial feasibility studies of dextran delivery systems utilized procaine hydrochloride as an inexpensive substitute for lysine vasopressin due to the higher loading capacity of dextrans compared to that of polystyrene. Procaine was sorbed or entrapped within the internal dextran matrices. Content uniformity improved as the procaine solution volume approached the liquid saturation level of the dextran particles. Drug release occurred rapidly and completely following immersion in aqueous media. Polymer coating of the procaine-loaded dextrans with hydroxypropyl methylcellulose phthalate (HPMCP) by coacervation did not provide adequate enteric properties. The coating process was evaluated by scanning electron microscopy and by "calcium-labeled" HPMCP with energy dispersive spectroscopy (EDS). EDS probing at various locations on several dextran particles gave calcium peaks indicating the presence of the coating. Based on release studies from coated dextrans, the coating was not sufficiently thick to provide enteric properties.