title: Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs.
abstract: OBJECTIVE
  The purpose of this research was to examine the pharmacokinetics (PK) of drug uptake for microneedle-based intradermal (ID) delivery of several classes of protein drugs compared to standard subcutaneous (SC) administration.
  
  
  METHODS
  Systemic absorption kinetics of various proteins were analyzed following microneedle-based ID delivery and standard injection methods in the swine model. Comparative PK data were determined using standard non-compartmental techniques based on blood serum levels.
  
  
  RESULTS
  Delivery of proteins using microneedles resulted in faster systemic availability, measured via t(max,) and increased maximal drug concentration, C(max,) over SC delivery for all proteins tested. Some agents also exhibited increased bioavailability for the ID route. Imaging studies using reporter dyes showed rapid lymphatic-mediated uptake.
  
  
  CONCLUSIONS
  Microneedle delivery is applicable to a wide variety of protein drugs and is capable of effective parenteral administration of therapeutic drug dosages. This delivery route alters absorption kinetics via targeting a tissue bed better perfused with lymphatic and blood vessels than the SC space. Microneedle delivery may afford various advantages, including a robust method to increase the absorption rate and bioavailability of proteins that have been challenging to deliver at therapeutic levels or with physiologically relevant profiles.
authors.affiliation: BD Technologies, 21 Davis Drive, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Harvey
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kaestner
authors.forename: Diane E
authors.initials: DE
authors.lastname: Sutter
authors.forename: Noel G
authors.initials: NG
authors.lastname: Harvey
authors.forename: John A
authors.initials: JA
authors.lastname: Mikszta
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Pettis
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D000068800:Etanercept; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood; D007271:Injections, Intradermal; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000378:metabolism*; D008845:Microinjections / Q000295:instrumentation / Q000379:methods*; D009339:Needles; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution
chemical_list: D007074:Immunoglobulin G; D007328:Insulin; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D000068800:Etanercept