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. Author manuscript; available in PMC: 2016 Dec 10.
Published in final edited form as: J Control Release. 2015 Oct 9;219:2–7. doi: 10.1016/j.jconrel.2015.10.005

Table 3.

Barriers to overcome by the 3G drug delivery systems.

Delivery Technology Formulation Barriers Biological Barriers
Poorly water-soluble drug delivery

  • New excipients for increasing drug solubility

  • Non-toxic to the body

  • No drug precipitation in the blood
Peptide/protein/nucleic acid delivery

  • Control of drug release kinetics

  • Control of drug loading

  • Control of therapeutic period

  • IVIVC

  • Long-term delivery up to a year

  • Non-invasive delivery
Targeted drug delivery using nanoparticles

  • Control of nanoparticle size, shape, surface chemistry, functionality, and flexibility.

  • Surface modification with ligands

  • Stimuli-sensitive delivery systems

  • Controlling biodistribution through altering vascular extravasation, renal clearance, metabolism, etc.

  • Navigating microenvironment of diseased tissues to reach target cells

  • Crossing endothelial barriers (e.g., blood-brain barrier)

  • Crossing mucosal barriers
Self-regulated drug delivery

  • Signal specificity & sensitivity

  • Fast responsive kinetics

  • Ability to stop drug release

  • Functional inside the body

  • Functional over the lifetime of drug delivery