Emerging innate biological properties of nano-drug delivery systems: A focus on PAMAM dendrimers and their clinical potential

Hadeel Kheraldine; Ousama Rachid; Abdella M Habib; Ala-Eddin Al Moustafa; Ibrahim F Benter; Saghir Akhtar

doi:10.1016/j.addr.2021.113908

Emerging innate biological properties of nano-drug delivery systems: A focus on PAMAM dendrimers and their clinical potential

Adv Drug Deliv Rev. 2021 Nov:178:113908. doi: 10.1016/j.addr.2021.113908. Epub 2021 Aug 11.

Authors

Hadeel Kheraldine¹, Ousama Rachid², Abdella M Habib³, Ala-Eddin Al Moustafa⁴, Ibrahim F Benter⁵, Saghir Akhtar⁶

Affiliations

¹ College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar; College of Pharmacy, QU Health, Qatar University, PO Box 2713, Doha, Qatar.
² Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar; College of Pharmacy, QU Health, Qatar University, PO Box 2713, Doha, Qatar.
³ College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar.
⁴ College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar; Biomedical Research Center, Qatar University, PO Box 2713, Doha, Qatar.
⁵ Faculty of Medicine, Eastern Mediterranean University, Famagusta, North Cyprus, Cyprus.
⁶ College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar. Electronic address: s.akhtar@qu.edu.qa.

PMID: 34390777
DOI: 10.1016/j.addr.2021.113908

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.

Keywords: Antimicrobial; Biological properties; Dendrimer; Diabetes; Drug delivery system; Nanotoxicology; PAMAM; Toxicity.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biological Availability
Dendrimers / chemistry
Dendrimers / metabolism*
Humans
Nanoparticle Drug Delivery System / chemistry*
Particle Size

Substances

Dendrimers
Nanoparticle Drug Delivery System
PAMAM Starburst