ABSTRACT
PURPOSE: The purpose of this work is to demonstrate the feasibility of using a proprietary technology called MicroCor™, based on solid-state, biodegradable microstructures (SSBMS), for transdermal delivery of macromolecules. METHODS: The proteins FITC-BSA (66 kDa) and recombinant protective antigen (rPA; 83 kDa) were incorporated into SSBMS arrays using a mold-based, liquid formulation casting and drying process. Arrays were applied to the skin with a custom applicator and then inspected to assess the extent of microstructure dissolution. In vitro FITC-BSA delivery to human cadaver skin was visualized using light and fluorescence microscopy and quantified by extracting and measuring the fluorescently labeled protein. rPA-containing SSBMS arrays were applied in vivo to Sprague-Dawley rats. The resulting serum IgG response was measured by ELISA and compared with responses elicited from intramuscular (IM) and intradermal (ID) routes of administration. RESULTS: FITC-BSA and rPA SSBMS arrays successfully penetrated the skin. Microstructure dissolution was observed over >95% of the array area and >75% of the microstructure length. FITC-BSA delivery correlated with protein content in the formulations. Antibody titers after transdermal delivery of rPA were comparable or higher than IM and ID titers. CONCLUSIONS: Transdermal delivery of macromolecules can be conveniently and effectively accomplished using the MicroCor technology.
Subject(s)
Antigens, Bacterial/administration & dosage , Biocompatible Materials/chemistry , Drug Delivery Systems/methods , Fluorescein-5-isothiocyanate/analogs & derivatives , Microinjections/instrumentation , Recombinant Proteins/administration & dosage , Serum Albumin, Bovine/administration & dosage , Administration, Topical , Animals , Drug Carriers/chemistry , Drug Delivery Systems/instrumentation , Enzyme-Linked Immunosorbent Assay , Equipment Design , Feasibility Studies , Female , Fluorescein-5-isothiocyanate/administration & dosage , Humans , Immunization/instrumentation , Immunization/methods , Immunoglobulin G/blood , Immunoglobulin G/immunology , In Vitro Techniques , Injections, Intradermal , Injections, Intramuscular , Microinjections/methods , Phase Transition , Rats , Rats, Sprague-Dawley , Skin/drug effects , Skin/metabolism , Technology, Pharmaceutical/methodsABSTRACT
The adsorption of four proteins, RNase A, HEWL, BSA, and beta-Lac, was examined on the surface of a negatively charged SiO(2)/TiO(2) optical waveguide. The amount of adsorbed protein followed the salt series Mg(2+)>Li(+)>Na(+)>K(+) and for anions Cl(-)>Br(-)>I(-). This ordering was attributed to protein adsorption being primarily influenced by changes in hydrophobic interactions between the surface and the protein resulting from differences in water structure arising from the presence of electrolytes.
Subject(s)
Electrolytes/chemistry , Proteins/metabolism , Water/chemistry , Adsorption/drug effects , Animals , Anions/chemistry , Buffers , Cations/chemistry , Cattle , Chickens , Hydrogen-Ion Concentration/drug effects , Hydrophobic and Hydrophilic Interactions , Lactoglobulins/metabolism , Models, Chemical , Muramidase/metabolism , Ribonuclease, Pancreatic/metabolism , Serum Albumin, Bovine/metabolism , Sodium Chloride/pharmacology , Solutions , Surface Properties/drug effectsABSTRACT
Sugar excipients are shown to reduce the adsorption of ribonuclease A, bovine serum albumin, and hen egg white lysozyme at the liquid-solid interface. The amount of protein adsorbed decreased as the concentration of the sugar increased. At the same sugar concentration, the ability of sugars to reduce protein adsorption followed the trend: trisaccharides > disaccharides > 6-carbon polyols > monosaccharides. This trend in adsorbed protein amounts among sugars was explained by stabilization of the protein native state in solution by the sugar excipients. The heat of solution of the amorphous saccharide was found to correlate with the amount of protein adsorbed.
