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A Perspective on Therapeutic Applications and Strategies to Mitigate Toxicity of Metallic Nanoparticles

Karuppaiah A, Selvaraj D, Sellappan M, Nagarajan A, Babu D, Rahman H, et al.

Curr Pharm Des, 2023;29(4):239-245.
PMID: 36624648 DOI: 10.2174/1381612829666230109111635

Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues. Hence, it is necessary to determine the possible undesirable effects of the MNPs after in-vivo application and exposure. One of the main reasons for the toxicity of MNPs is the release of their respective metallic ions throughout the body. Many research studies are in progress investigating the various strategies to reduce the toxicity of MNPs. These research studies aim to change the size, dose, agglomeration, release, and excretion rates of MNPs. In this perspective review, we discussed the possible strategies to improve the therapeutic effects of MNPs through various processes, with lessons learned from the studies involving silver nanoparticles (AgNPs). We also discussed the ways to manage the toxicity of MNPs by purification, surface functionalization, synergistic effect, and targeted therapy approach. All these strategies could reduce the dose of the MNPs without compromising their therapeutic benefits, which could decrease the toxicity of MNPs. Additionally, we briefly discussed the market and toxicology testing for FDA-regulated MNPs.
Fabrication of Mastic Gum Resin Tethered Phospholipid Nanocarriers for the Evaluation and Enhancement of Anti-inflammatory and Anti-bacterial Effects

Selvaraj K, Lee SJ, Song KB, Yoo BK, Karuppaiah A

Curr Pharm Des, 2025 Jan 28.
PMID: 39878118 DOI: 10.2174/0113816128353794241225083428

INTRODUCTION: The objective of the present study was to improve the anti-inflammatory and antibacterial activities of mastic gum resin (MGR). MGR was loaded into a phospholipid nanocarrier with or without partially hydrolyzed ginsenoside, followed by dispersion into distilled water.
METHOD: The phospholipid nanocarrier dispersion showed significantly enhanced in-vitro release, porcine skin/ intestine permeation, and retention. When the ratio of the MGR versus partially hydrogenated ginsenoside reached 1:1 w/w in the nanocarrier composition, the in-vitro release increased 54.8-fold compared to the MGR powder suspended in the release media.
RESULTS: Permeation of the nanocarrier dispersion through the porcine skin and intestine increased 160-fold and 42-fold, respectively, compared to permeation of the MGR powder suspension. Furthermore, the nanocarrier dispersion reduced NO production and iNOS mRNA expression in the LPS-stimulated RAW264.7 cells. MIC and MBC of the nanocarrier dispersion against P. gingivalis were 4.11 ± 1.17 and 8.22 ± 2.35 μg/mL, respectively.
CONCLUSION: In conclusion, the anti-inflammatory and antibacterial activities of MGR were remarkably enhanced when the MGR was loaded into the nanocarrier with partially hydrolyzed ginsenoside.

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