Exploration of inorganic nanoparticles for revolutionary drug delivery applications: a critical review

Abstract

The nanosystems for delivering drugs which have evolved with time, are being designed for greater drug efficiency and lesser side-effects, and are also complemented by the advancement of numerous innovative materials. In comparison to the organic nanoparticles, the inorganic nanoparticles are stable, have a wide range of physicochemical, mechanical, magnetic, and optical characteristics, and also have the capability to get modified using some ligands to enrich their attraction towards the molecules at the target site, which makes them appealing for bio-imaging and drug delivery applications. One of the strong benefits of using the inorganic nanoparticles-drug conjugate is the possibility of delivering the drugs to the affected cells locally, thus reducing the side-effects like cytotoxicity, and facilitating a higher efficacy of the therapeutic drug. This review features the direct and indirect effects of such inorganic nanoparticles like gold, silver, graphene-based, hydroxyapatite, iron oxide, ZnO, and CeO₂ nanoparticles in developing effective drug carrier systems. This article has remarked the peculiarities of these nanoparticle-based systems in pulmonary, ocular, wound healing, and antibacterial drug deliveries as well as in delivering drugs across Blood-Brain-Barrier (BBB) and acting as agents for cancer theranostics. Additionally, the article sheds light on the plausible modifications that can be carried out on the inorganic nanoparticles, from a researcher's perspective, which could open a new pathway.

Keywords: Blood–brain-barrier; Drug delivery; Inorganic nanoparticles; Theranostics; Wound healing.

Fig. 1

A TEM/SEM images of various inorganic nanoparticles having different morphologies. (a) Au nanorods, (b) Au nanorattles, (c) Au nanostars, (d) Ag nanospheres, (e) Ag nanoprisms, and (f) ZnO nanoflowers. (b–e) adapted with permission from [118, 119] and [120]. Copyright 2019, 2015, 2021 American Chemical Society. (a) and (f) adapted with permission from [121] and [122]. © 2023, 2019 Elsevier Ltd. All rights reserved. B The AuNPs inside the HepG2 cells treated with the AuNPs—lipoic acid—modified PEG derivative of DOX: a) in the presence and absence of various inhibitors and b) at 4 h or 12 h. c) The TEM images of HepG2 cells with: (i) citrate protected AuNPs and (ii) AuNPs—lipoic acid—modified PEG derivative of DOX for 4 h or 12 h. d) Cell viability plot. Adapted with permission from [54]. Copyright 2017 American Chemical Society. C Different biomedical applications of Iron Oxide nanoparticles

Fig. 2

A Administration of drugs into lungs using nanoparticle-based drug carriers. B (a) Cytotoxicity of GO, GO-PEG and GO-PEG-MAN on human THP-1 cells. (b) Cellular uptake of C6@GO-PEG and C6@GO-PEG-MAN by THP-1 cells after 1 h incubation. (c) Effects of free mannose on the cellular uptake of C6@GO-PEG-MAN in THP-1 cells. (d) Cellular uptake of C6@GOPEG-MAN in THP-1 cells under different endocytosis inhibition conditions. (e) Confocal images for intracellular localization of C6@GO-PEG-MAN and lysosomes in THP-1 cells at 1 h, 3 h, 6 h and 12 h. TEM images for localization of (f, g) GO-PEG-MAN in lysosomes of THP-1 cells, and (h, i) GO-PEG-MAN and M.tuberculosis (H37Rv) in the H37Rv infected THP-1 cells. Adapted with permission from [164]. © 2019 Elsevier Ltd. All rights reserved. C) (a) Cellular uptake of [⁴⁶Sc] Sc-HAp and [⁴⁶Sc] Sc-HAp-Zr in A549 cell line at 10, 30, and 60 min. (b) Ex vivo biodistribution of Sc-46, [⁴⁶Sc] Sc-HAp, and [⁴⁶Sc] Sc-HAp-Zr in normal mice 1 h after injection. Adapted with permission from [165]. © 2021 Elsevier Ltd. All rights reserved

Fig. 3

A (a) TEM image of Au nanorattles enclosed within chitosan. (b-e) Fluorescence microscopy images of Acridine orange/ethidium bromide dual staining of MCF-7 cells treated with 200 μgml⁻¹ of the nanocarriers under different conditions: (b) control, (c) CS-Au nanorattles-DOX without laser, (d) CS-Au nanorattles-DOX with NIR laser. (f-i) SEM images of MCF-7 cell apoptosis: (f) untreated; (g-i) MCF-7 cells treated with 200 μgml⁻¹ CS-Au nanorattles-DOX irradiated with 785 nm NIR laser. Adapted with permission from [118]. Copyright 2019 American Chemical Society. B (a) In vivo fluorescence images of MDA-MB-231 tumor-bearing mice captured at 1 h, 3 h, 6 h, and 24 h post-injection of Cy3-labeled HGP21, HGPscr or P21. (b) Fluorescence intensity of each tumor site by region of interest analysis. (c) Fluorescence intensity of isolated organs from each group at 24 h post-injection. (d) Ex vivo fluorescence images of isolated tumors, and their tissue sections using confocal microscopy (e) Observation of apoptotic activity in each tumor section of nanoparticles-injected mouse, by TUNEL assay. Adapted with permission from [186]. © 2017 Elsevier Ltd. All rights reserved

Fig. 4

A The transportation of large and small nanocarriers across the BBB. B Effect of the AgNPs entrapped PNP-CTX on both the irradiated and non-irradiated U87MG cells and the tumor viability. (A) MTT assay of varying concentrations of nanoconstructs for 72 h. (B) In situ apoptosis detection and the corresponding quantification of the apoptotic bodies in U87MG cryosections from the non-irradiated and irradiated mice, injected with AgNPs entrapped PNP-CTX. C Luciferase imaging of the representative mice. D Plot representing the tumor growth during 11 days of observation. Adapted with permission from [222]. Copyright 2016 American Chemical Society. C (a) TEM image of SPIONs-PVA loaded liposome (40,000X). (b) Graph explaining the superparamagnetic properties of the prepared SPIONs-PVA, liposome and SPIONs-PVA-loaded liposome. (c, d) SPIONs accumulation detection by T1 and T2-weight MRI in mice bearing intracranial lymphoma xenografts. Adapted with permission from [223]. Copyright 2017 American Chemical Society

Fig. 5

A Various methods of administration of drug-loaded nanocarriers to overcome different ocular barriers B (a) Image of the AuNPs loaded contact lens. (b) Timolol concentration in tear fluid from the blank-4 mg contact lenses (253 ± 3 μg timolol loading), 0.025 mM-GNP-CL-4 mg (277 ± 7 μg timolol loading) and eye drop treatment (1 drop = 250 μg of timolol maleate). The histopathological images of cornea were taken by the light microscopy at X450 magnification. Adapted with permission from [239]. © 2019 Elsevier Ltd. All rights reserved

Fig. 6

A (a) The effect of delivery of naked anti-microbial nanoparticles and drug conjugated nanoparticles to the wound site by various methods. (b) The mechanism of antimicrobial activity of anti-microbial nanoparticles. B (a) Photograph of the PAA@rGO electrospun polymeric mat. (b, c) SEM images of S. epidermidis treated with cefepime loaded PAA@rGO mats and irradiation for 5 min and 30 min, respectively. Photographs of (d) wound scars, 24 h after photothermal treatment for 10 min and (e) intact mouse skin and the three representative skin samples after 48 h of infection, under different treatment conditions. Adapted with permission from [256]. Copyright 2018 American Chemical Society. C (a) The confocal images of (i) S. aureus and (ii) E. coli, respectively treated with ZnO and ZnO-CS/Alg. (b) Histological analysis on HE stains and on Masson’s trichrome stain of the ZnO-CS/Alg. group at (i, vi) 3 days, (ii, vii) 7 days, (iii, viii) 14 days, (iv, ix) 21 days, and (v, x) 48 days, respectively. Adapted with permission from [257]. © 2019 Elsevier Ltd. All rights reserved