Table 1

Advantages and disadvantages of different routes of administration for drug delivery formulations relevant to infectious diseases

Route of administrationSite of absorptionExamples of drug delivery formulationsAdvantagesDisadvantages
Enteral
 Oral (per os)Along gastrointestinal tractIngestible gastric resident systems for antimalarials and antiretrovirals6 7

  1. Non-invasive.

  2. Can be self-administered.

  3. Preferred by patients.

  1. Non-adherence due to frequent dosing for high pill burden of TB treatment.

  2. Chemical environment is harsh.

  3. Degraded by first pass-metabolism.

Solid lipid nanoparticles of TB treatment9
Paediatric dispersible tablets for Coartem and delaminid16 17
 Sublingual or buccalSurfaces in the mouthMetered sublingual spray of artemether (ArTiMist) for children18

  1. Non-invasive.

  2. Can be self-administered.

  3. Rapid absorption.

  4. Avoids first-pass metabolism.

  1. Low surface area for absorption which limits dose and may not be in line with gram-level dosing of TB treatment.

  2. Bitter taste of drugs.

  3. Prone to irritation of oral mucosa.

 RectalRectal mucosaRectal artesunate suppositories for the prereferral management of severe malaria19

  1. Useful for unconscious patients and children.

  2. No need to taste-mask drug.

  3. Partial avoidance of first-pass metabolism.

  1. Absorption can be slow or erratic.

  2. Frequent application to match gram-level dosing of TB treatment.

  3. Prone to irritation of rectal mucosa.

Parental
 IntravenousVeins, systemic bioavailableArtemisinin nanoformulation20

  1. Achieves 100% bioavailability.

  2. Reproducible.

  1. Invasive.

  2. Requires trained personnel.

  3. Prone to infection.

  4. Frequent injections to match gram-level dosing of TB treatment.

 IntramuscularSkeletal muscleNanoparticles of rilpivirine and cabotegravir for HIV treatment21

  1. Rapid absorption.

  2. Avoids first-pass metabolism.

  1. Invasive.

  2. Limited volume for injection, so may not match gram-level dosing of TB treatment.

  3. Risk of nerve damage.

Atovaquone solid drug nanoparticles for malaria prophylaxis22
 SubcutaneousInto tissue between dermis and muscleUltra-long-acting dolutegravir implant for HIV treatment and prevention23

  1. Slow absorption and distribution compared with intramuscular.

  2. Avoids first-pass metabolism.

  1. Invasive.

  2. Limited volume for injection, so may not match gram-level dosing of TB treatment.

  3. Risk of tissue damage.

Nanochannel implant with refillable feature for delivery of tenofavir diphosphate24
 IntradermalInto dermis layerIntradermal injections of HIV DNA vaccines using needle-free injector25

  1. Faster absorption and distribution compared with subcutaneous.

  2. Avoids first-pass metabolism.

  3. Higher immune responses for vaccinations.

  1. Invasive.

  2. Limited volume for injection, so may not match gram-level dosing of TB treatment.

  3. Risk of tissue damage.

 IntrathecalInto cerebrospinal fluidIntrathecal administration of isoniazid for TB meningitis treatment26

  1. Bypasses blood–brain barrier.

  2. Local effect on meninges or cerebrospinal axis.

  1. Invasive.

  2. Limited volume for injection, so may not match gram-level dosing of TB treatment.

  3. Risk of tissue damage.

 Intra-articularInto joint spaceIntra-articular streptomycin in tuberculosis of the knee27

  1. Avoids first-pass metabolism.

  2. Local effect on joint.

  1. Invasive.

  2. Limited volume for injection, so may not match gram-level dosing of TB treatment.

  3. Risk of tissue damage.

 InhalationMucosal surfaces for the lungNebulised solid lipid nanoparticles for TB treatment10

  1. Non-invasive.

  2. Large surface area for absorption.

  3. Avoids first-pass metabolism.

  4. Targets where TB bacteria reside.

  1. Variability in dosing depends on patient technique.

  2. Requires portable, cheap and easy to operate devices for administration.

  3. Frequent inhalation to be compatible with gram-level dosing of TB treatment.

Nano microparticle vaccine formulation for TB28
 TransdermalThrough skinFilm of HIV inhibitor IQP-041029

  1. Non-invasive.

  2. Can be self-administered.

  3. Avoids first-pass metabolism.

  1. Transport barriers for many drugs.

  2. Slow absorption.

  3. May require frequent administration or very large patch to match gram-level dosing of TB.

 Solid dispersions of artemisinin for malaria treatment30
 Topical: ocular, nasal, skinAt site of applicationTopical treatment of cutaneous TB using oil nanoemulsions31

  1. Non-invasive.

  2. Can be self-administered.

  3. Rapid absorption.

  4. Local effect, so avoids side effects.

  1. Transport barriers for many drugs.

  2. May require frequent administration to match gram-level dosing of TB.

 Intravaginal
 		Mucosal surfaces lining the vaginaMonthly vaginal rings for dapivirine, an HIV drug32

  1. Reduce frequency of dosing.

  2. Avoids first-pass metabolism.

  3. Dense network of blood vessels in vagina, so ideal for systemic drug absorption.

  1. Invasive.

  2. Requires trained personnel.

  3. Implants may require frequent dosing to match gram-level dosing of TB treatment.

Topical tenofovir disoproxil fumarate nanoparticles33

  • TB, tuberculosis.