Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs

Pharm Res. 2011 Jan;28(1):107-16. doi: 10.1007/s11095-010-0123-9. Epub 2010 Mar 31.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Equipment Design
  • Etanercept
  • Female
  • Human Growth Hormone / administration & dosage
  • Human Growth Hormone / blood
  • Human Growth Hormone / pharmacokinetics
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / blood
  • Injections, Intradermal
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / pharmacokinetics
  • Lymph Nodes / metabolism*
  • Microinjections / instrumentation
  • Microinjections / methods*
  • Needles*
  • Receptors, Tumor Necrosis Factor / administration & dosage
  • Receptors, Tumor Necrosis Factor / blood
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / blood
  • Recombinant Proteins / pharmacokinetics*
  • Skin / metabolism
  • Swine
  • Swine, Miniature
  • Tissue Distribution

Substances

  • Immunoglobulin G
  • Insulin
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Human Growth Hormone
  • Etanercept