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Table 5 Summary of different types of administration routes for mRNA delivery

From: mRNA nanodelivery systems: targeting strategies and administration routes

Administration Routes

Advantages

Disadvantages

Target organs/cells

Intravenous administration

Common methods of mRNA therapy Rapid onset of action High bioavailability mRNA NPs can be directly delivered to the systemic circulation

Invasive

Extrahepatic targeting difficulty

Immunogenicity

Liver

Lung

Spleen

Lymph node

Fetus

Intramuscular (i.m.) administration

Common method of vaccine administration Convenient Avoids first-pass metabolism

Invasive

Painful

Immune cells

Subcutaneous (s.c.) administration

Convenient

Avoids first-pass metabolism

Invasive Painful

Immune cells

Intradermal (i.d.) administration

Efficient delivery of small doses Minimal tissue damage

Invasive Painful

Immune cells

Microneedles (MNs)

Non-invasive

Painless

Simple operation

Convenient storage

Avoids first-pass metabolism

Specialized equipment required

Immune cells

Needle-free injection (NFI)

Non-invasive

Painless

Simple operation

Avoids first-pass metabolism

Contact areas between drugs and capillaries increased

Specialized equipment required

Immune cells

Intranasal administration

Aon-invasiveRapid onset of actionAvoids first-pass metabolism

Precisely targeting the lungs

Bypass the BBB and reach the central nervous system

Overcome barriers in respiratory tracts

Lung

Brain

Oral administration

Non-invasive

Convenient

Easy to administer

Overcome barriers in gastrointestinal tract

Low bioavailability

first-pass metabolism

Gastrointestinal tract

Vaginal nebulization

Non-invasive

Avoids first-pass metabolism

Higher drug concentration with reduced dosage

Limited to female

Vagina

Immune cells

Intravesical instillation

High local drug concentration

Avoids systemic side effects

Sustained release

Invasive

Limited to bladder-related conditions

Bladder tissues

Orthotopic injection

Avoids some unique tissue barriers

Precise delivery to target organ

Avoids systemic side effects

Invasive

Requires specialized expertise

Brain

Eyes

Fetus