Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules

Eur J Pharm Biopharm. 2014 Sep;88(1):8-27. doi: 10.1016/j.ejpb.2014.03.004. Epub 2014 Mar 28.


As a non-invasive route, intranasal administration offers patient comfort and compliance which are hurdled in parenteral drug therapy. In addition, the current recognition that the high permeability and vascularization of nasal mucosa coupled to the avoidance of the first-pass elimination and/or gastrointestinal decomposition ensure higher systemic drug absorption than oral route has contributed to the growing interest for intranasal delivery of drugs that require considerable systemic exposure to exert their therapeutic actions (systemic-acting drugs). Nevertheless, several features may hamper drug absorption through the nasal mucosa, particularly the drug molecular weight and intrinsic permeability, and, therefore, several strategies have been employed to improve it, propelling a constant challenge during nasal drug (formulation) development. This review will firstly provide an anatomical, histological and mechanistic overview of drug systemic absorption after nasal administration and the relevant aspects of the therapeutic interest and limitations of the intranasal systemic delivery. The current studies regarding the nasal application of systemic-acting small drugs (analgesic drugs, cardiovascular drugs and antiviral drugs) and biomacromolecular drugs (peptide/protein drugs and vaccines) will also be outlined, addressing drug pharmacokinetics and pharmacodynamic improvements.

Keywords: Biomacromolecule; Intranasal delivery; Nasal route; Pharmacokinetics; Small-molecule drugs; Systemic-acting drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Intranasal*
  • Administration, Oral
  • Analgesics / administration & dosage
  • Animals
  • Antiviral Agents / administration & dosage
  • Biological Transport
  • Calcitonin / administration & dosage
  • Cardiovascular Agents / administration & dosage
  • Deamino Arginine Vasopressin / administration & dosage
  • Drug Delivery Systems
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Humans
  • Insulin / administration & dosage
  • Molecular Weight
  • Nasal Mucosa / drug effects*
  • Oxytocin / administration & dosage
  • Peptides / administration & dosage
  • Pharmaceutical Preparations / administration & dosage*
  • Proteins / administration & dosage
  • Salmon
  • Vaccines / administration & dosage


  • Analgesics
  • Antiviral Agents
  • Cardiovascular Agents
  • Insulin
  • Peptides
  • Pharmaceutical Preparations
  • Proteins
  • Vaccines
  • Gonadotropin-Releasing Hormone
  • Oxytocin
  • Calcitonin
  • Deamino Arginine Vasopressin