Transdermal delivery of macromolecules using solid-state biodegradable microstructures.
OBJECTIVE
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.
Corium International, Inc., 235 Constitution Drive, Menlo Park, California 94025, USA.
Janet R
JR
Wendorf
Esi B
EB
Ghartey-Tagoe
Stephen C
SC
Williams
Elena
E
Enioutina
Parminder
P
Singh
Gary W
GW
Cleary
D000287:Administration, Topical; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D004867:Equipment Design; D005240:Feasibility Studies; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007114:Immunization / Q000295:instrumentation / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008845:Microinjections / Q000295:instrumentation* / Q000379:methods; D044367:Phase Transition; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
D000942:Antigens, Bacterial; D001672:Biocompatible Materials; D004337:Drug Carriers; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate