Abstract
Drug delivery systems or vectors are usually needed to improve the bioavailability and effectiveness of a drug through improving its pharmacokinetics/pharmacodynamics at an organ, tissue or cellular level. However, emerging technologies with sensitive readouts as well as a greater understanding of physiological/biological systems have revealed that polymeric drug delivery systems are not biologically inert but can have innate or intrinsic biological actions. In this article, we review the emerging multiple innate biological/toxicological properties of naked polyamidoamine (PAMAM) dendrimer delivery systems in the absence of any drug cargo and discuss their correlation with the defined physicochemical properties of PAMAMs in terms of molecular size (generation), architecture, surface charge and chemistry. Further, we assess whether any of the reported intrinsic biological actions of PAMAMs such as their antimicrobial activity or their ability to sequester glucose and modulate key protein interactions or cell signaling pathways, can be exploited clinically such as in the treatment of diabetes and its complications.
Highlights
The effectiveness of a pharmacological agent is dependent on its ability to reach the right target organ, tissue or intracellular site of action in an intact or active form for a sufficient period of time to exert the desired biological activity
It is becoming increasingly apparent that PAMAM dendrimer nanoparticles exhibit innate or intrinsic biological properties beyond their ability to improve drug delivery as has been highlighted in this review
In addition to the usual dose and time dependency, the biological effects of PAMAMs were dependent on the dendrimer generation, surface charge/chemistry, structural architecture and the cell or biological system studied
Summary
The effectiveness of a pharmacological agent (e.g. drug or vaccine) is dependent on its ability to reach the right target organ, tissue or intracellular site of action in an intact or active (right) form for a sufficient (right) period of time to exert the desired (right) biological activity. Delivery systems can often be needed for classical small molecule drugs They will be required for delivering the more recently developed macromolecular gene editing technologies such as CRISPR/Cas (clustered interspaced short palindromic repeats/CRISPR-associated protein 9) that are undergoing human clinical trials evaluation [25,26,27,28]. We further assess whether any of the reported intrinsic biological actions of PAMAMs such as their antimicrobial activity or their ability to sequester glucose and modulate key protein interactions and cell signaling pathways, can be exploited clinically (e.g. in the treatment of diabetes and its complications)
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