Molecular charge mediated transport of a 13 kD protein across microporated skin.
Transport of proteins across the skin is highly limited owing to their hydrophilic nature and large molecular size. This study was conducted to assess the skin transport abilities of a model protein across hairless rat skin during iontophoresis alone and in combination with microneedles as a function of molecular charge. The effect of microneedle pretreatment on electroosmotic flow was also investigated. Skin permeation experiments were carried out in vitro using daniplestim (DP) (MW, 12.76 kD; isoelectric point, 6.2) as a model protein molecule. The effect of molecular charge on protein transport was evaluated by performing studies in two different buffers--TRIS (pH 7.5) and acetate (pH 4.0). Iontophoretic transport mechanisms of DP varied with respect to molecular charge on the protein. The combination approach (iontophoresis and microneedles) gave much higher flux values compared to iontophoresis alone at both pH 4.0 and pH 7.5, however, the delivery in this case was also found to be charge dependent. The findings of this study indicate that electroosmosis persisted upon microporation, thus retaining skin's permselective properties. This enables us to explore the combination of microneedles and iontophoresis as a potential approach for delivery of proteins.
Katikaneni
Sahitya
S
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341, USA.
Badkar
Advait
A
Nema
Sandeep
S
Banga
Ajay K
AK
D000279:Administration, Cutaneous; D000818:Animals; D001692:Biological Transport; D002021:Buffers; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007478:Iontophoresis; D007526:Isoelectric Point; D008297:Male; D008845:Microinjections; D009339:Needles; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D010539:Permeability; D051381:Rats; D012869:Skin Absorption
D002021:Buffers; D007377:Interleukin-3; D010446:Peptide Fragments; C093340:daniplestim