Exploration of inorganic nanoparticles for revolutionary drug delivery applications: a critical review
Discover Nano · 5 authors, 2 centres
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This critical review examines the potential of inorganic nanoparticles (gold, silver, graphene, iron oxide, zinc oxide, cerium oxide, and hydroxyapatite) for drug delivery, highlighting their superior stability, tunable properties, and high drug loading capacity compared to organic nanoparticles. The paper summarizes recent research developments in using these nanoparticles for pulmonary, cancer theranostic, blood-brain barrier, ocular, and wound healing applications, emphasizing their ability to improve therapeutic efficacy and reduce side effects. The clinical significance lies in the growing number of FDA-approved inorganic nanoparticle formulations, though challenges such as toxicity, stability, and regulatory hurdles remain.
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**Background:** Conventional drug delivery methods face limitations such as poor drug loading efficiency, rapid release, and difficulty in targeting specific sites. Inorganic nanoparticles offer advantages over organic nanoparticles, including enhanced stability, tunable degradation rates, and superior drug loading capacity. This review critically evaluates the recent developments in using various inorganic nanoparticles for drug delivery applications.
**Methods:** The authors conducted a narrative review of the literature, focusing on gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), graphene derivatives, iron oxide nanoparticles (IONPs), zinc oxide nanoparticles (ZnO NPs), cerium oxide nanoparticles (CeO2 NPs), and hydroxyapatite (HAp) nanoparticles. They summarized recent research (primarily from 2015-2023) on the synthesis, functionalization, and application of these nanoparticles for drug delivery across different therapeutic areas.
**Key Results:** The review presents numerous examples of inorganic nanoparticle-based drug delivery systems:
- **Gold nanoparticles (AuNPs):** AuNPs functionalized with lipoic acid-modified PEG and doxorubicin (DOX) doubled drug concentration in tumor cells compared to DOX-HCl. AuNPs loaded with ketotifen in contact lenses showed controlled release up to 96 hours. AuNPs of 10 nm size were the only ones able to cross the blood-brain barrier (BBB) in a glioblastoma mouse model.
- **Silver nanoparticles (AgNPs):** AgNPs/polyacrylamide/dextran with ornidazole showed 98.5% in-vitro drug release at 6 hours. AgNPs functionalized with folate and thiolated chitosan loaded with docetaxel (DTX) displayed higher anti-cancer activity (IC50 = 0.062 µg/ml) compared to DTX-NCPs (0.536 µg/ml).
- **Graphene derivatives:** GO/PEG nanocarriers achieved 81% loading efficiency for DOX. GO/chitosan loaded with caffeic acid showed drug release that did not reach zero even after 7 days. GO-PEG-MAN loaded with rifampicin showed 79.92 ± 1.72% release at pH 5.5 in 48 hours, compared to 53.62 ± 1.28% at pH 7.4.
- **Iron oxide nanoparticles (IONPs):** SPIONs (superparamagnetic IONPs) of 10-20 nm exhibit superparamagnetic properties ideal for drug delivery. IONPs-HAp nanorods loaded with curcumin showed better cellular uptake than free curcumin.
- **Zinc oxide nanoparticles (ZnO NPs):** ZnO/PVP loaded with pilocarpine hydrochloride showed sustained release for 14 days for glaucoma treatment.
- **Cerium oxide nanoparticles (CeO2 NPs):** Nanoceria functionalized with ZM241385 and chitosan for glaucoma treatment established 42 times longer period to normalize elevated intraocular pressure in a one-time administration.
- **Hydroxyapatite (HAp):** Zr-doped HAp nanoparticles for lung cancer therapy had an IC50 value of 513 µg/ml. Honokiol-loaded HAp nanoparticles reduced tumor size by 40% in in-vivo glioma studies.
**Clinical Implications:** The review highlights that over 100 nanoparticle-based formulations are on the market as of 2022, with AgNPs accounting for 57% of commercial products. FDA-approved examples include dextran-coated SPIONs (Feridex®/Endorem®) for imaging and AgNP-containing wound dressings (PolyMem Silver™, Aquacel™, Tegaderm™). However, challenges remain, including potential toxicity (e.g., AuNP toxicity depends on shape, size, and surface charge; GO sheets can cause dose-dependent cytotoxicity), stability issues, and the need for scalable production. The authors emphasize that future research should focus on developing "smart" nanoparticles responsive to pH, light, or temperature, and on establishing regulatory guidelines specific to nanoparticle-based drug carriers.