Table 1.

Advantages and disadvantages of drug loading methods.

Methods	Advantages	Disadvantages
Embedded in the cavity of PAMAM	Suitable for small-molecule, hydrophobic drugs, such as DOX, ATO; Improves solubility of hydrophobic drugs; Avoids burst release; Enhances bioavailability of insoluble drugs.	Not suitable for small-molecule hydrophilic or macromolecular hydrophobic drugs; Low drug responsiveness to specific environments.
Complexed on the surface of PAMAM	Avoids nucleic acid (such as RNA) degradation by nucleases; Decreases the surface charge of PAMAM; Improves transfection efficiency; Enhances brain targeting.	Only suits ionizable drugs, such as ibuprofen, siRNA; Instability of drug–PAMAM complexes once environment, such as pH, changes.
Covalently bound in the arm of PAMAM	Suitable for drugs with reactive groups; Increases the stability of binding drugs; Responsive and controlled drug release.	Decreases water solubility of PAMAM when bound with hydrophobic drugs; Requires activating reagents and specific reaction conditions.