title: Development of a codrug approach for sustained drug delivery across microneedle-treated skin.
abstract: Microneedle (MN) enhanced transdermal drug delivery enables the transport of a host of molecules that cannot be delivered across the skin by passive diffusion alone. However, the skin being a self-regenerating organ heals itself and thus prevents delivery of molecules through micropores for a 7-day time period, the ideal transdermal delivery goal. Hence, it is necessary to employ a second drug molecule, a cyclooxygenase inhibitor to enhance pore lifetime by decreasing local subclinical inflammatory response following MN treatment. A codrug approach using a 3-O-ester codrug of the model drug naltrexone (NTX) with diclofenac (DIC), a cyclooxygenase inhibitor, was tested in vitro as well as in vivo to look at stability, bioconversion and permeation. The results indicated that the approach could be useful for transdermal drug delivery of NTX from a single patch for a week, but stability and solubility optimization will be required for the codrug before it can deliver significant levels of NTX into the plasma. The skin concentration of DIC was high enough to keep the pores open in vivo in a hairless guinea pig model as demonstrated by day seven pore visualization studies.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.
authors: Priyanka
authors: P
authors: Ghosh
authors: Raghotham R
authors: RR
authors: Pinninti
authors: Dana C
authors: DC
authors: Hammell
authors: Kalpana S
authors: KS
authors: Paudel
authors: Audra L
authors: AL
authors: Stinchcomb
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D004008:Diclofenac / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006168:Guinea Pigs; D009271:Naltrexone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009339:Needles; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D057968:Transdermal Patch
chemical_list: D016861:Cyclooxygenase Inhibitors; D009292:Narcotic Antagonists; D004008:Diclofenac; D009271:Naltrexone