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. 2023 Jul 21;15(7):1998.
doi: 10.3390/pharmaceutics15071998.

Delicate Hybrid Laponite-Cyclic Poly(ethylene glycol) Nanoparticles as a Potential Drug Delivery System

Shengzhuang Tang  1 , Jesse Chen  1 , Jayme Cannon  1 , Mona Chekuri  1 , Mohammad Farazuddin  1   2 , James R Baker Jr  1   2 , Su He Wang  1   2
Affiliations

Delicate Hybrid Laponite-Cyclic Poly(ethylene glycol) Nanoparticles as a Potential Drug Delivery System

Shengzhuang Tang et al. Pharmaceutics. .

Abstract

The objective of the study was to explore the feasibility of a new drug delivery system using laponite (LAP) and cyclic poly(ethylene glycol) (cPEG). Variously shaped and flexible hybrid nanocrystals were made by both the covalent and physical attachment of chemically homogeneous cyclized PEG to laponite nanodisc plates. The size of the resulting, nearly spherical particles ranged from 1 to 1.5 µm, while PEGylation with linear methoxy poly (ethylene glycol) (mPEG) resulted in fragile sheets of different shapes and sizes. When infused with 10% doxorubicin (DOX), a drug commonly used in the treatment of various cancers, the LAP-cPEG/DOX formulation was transparent and maintained liquid-like homogeneity without delamination, and the drug loading efficiency of the LAP-cPEG nano system was found to be higher than that of the laponite-poly(ethylene glycol) LAP-mPEG system. Furthermore, the LAP-cPEG/DOX formulation showed relative stability in phosphate-buffered saline (PBS) with only 15% of the drug released. However, in the presence of human plasma, about 90% of the drug was released continuously over a period of 24 h for the LAP-cPEG/DOX, while the LAP-mPEG/DOX formulation released 90% of DOX in a 6 h burst. The results of the cell viability assay indicated that the LAP-cPEG/DOX formulation could effectively inhibit the proliferation of A549 lung carcinoma epithelial cells. With the DOX concentration in the range of 1-2 µM in the LAP-cPEG/DOX formulation, enhanced drug effects in both A549 lung carcinoma epithelial cells and primary lung epithelial cells were observed compared to LAP-mPEG/DOX. The unique properties and effects of cPEG nanoparticles provide a potentially better drug delivery system and generate interest for further targeting studies and applications.

Keywords: PEGylation of laponite; drug delivery; functional cyclized polyethylene glycol; hybrid nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Representation of a sheet of laponite (LAP) changed to LAP-NH2.
Scheme 2
Scheme 2
Synthesis of functional cyclic PEG (cPEG-OH).
Scheme 3
Scheme 3
Representation of covalent attachment of cyclic PEG to LAP.
Scheme 4
Scheme 4
Representation of covalent attachment of linear mPEG to LAP.
Figure 1
Figure 1
13C NMR spectra (a), and 1H NMR spectra (b) of PEG, cPEG-OH, and cPEG-NP in deuterated chloroform CDCl3.
Figure 2
Figure 2
Representative mass spectra of PEG and cPEG-OH (a); gel permeation chromatography traces of mPEG, PEG, and cPEG-OH (b).
Figure 3
Figure 3
FTIR spectra (a) and 1H NMR spectra (b) of LAP, LAP-NH2, cPEG-OH, and LAP-cPEG.
Figure 4
Figure 4
Scanning electron micrographs of LAP-cPEG and LAP-mPEG at magnifications of ×500 (a-1,b-1) and ×15 000 (a-2,b-2).
Figure 5
Figure 5
Dynamic light scattering for LAP, LAP–NH2, LAP–mPEG, and LAP−cPEG at the same concentration of 0.05 mg/mL: hydrodynamic size (a) and zeta potential (b).
Figure 6
Figure 6
UV–Vis spectra (a) and UPLC chromatogram (UV traces at 480 nm) (b) representative of aqueous solutions of LAP-cPEG, DOX, and LAP-cPEG/DOX.
Figure 7
Figure 7
In vitro release profile from a dialysis bag of DOX in the free form, LAP-cPEG/Dox formulation in the presence of PBS or human plasma, and LAP-mPEG/DOX formation in human plasma (a); in vitro XTT cell viability assay of A549 cells treated with free DOX, LAP-mPEG/DOX, and LAP-cPEG/DOX at different DOX concentrations for 48 h (b).
Figure 8
Figure 8
XTT assay results summary of A549 cells treated with DOX, LAP-mPEG/DOX, and LAP-cPEG/DOX at DOX concentrations of 0.75, 1, and 1.25 µM The viability of the cells treated with LAP-cPEG/DOX was significantly decreased compared to those treated with LAP-mPEG/DOX (* p < 0.05; ** p < 0.01).
Figure 9
Figure 9
Evaluation of apoptosis in A549 cells by 7-AAD assay after 24 h of treatment with DOX, LAP-mPEG/DOX, and LAP-cPEG/DOX. As shown, there was a significant increase in the number of apoptotic cells treated with the LAP-cPEG/DOX formulation compared to the LAP-mPEG/DOX at a DOX concentration of 1.25 µM (*** p < 0.001).
Figure 10
Figure 10
Evaluation of apoptosis in primary lung cells by EpCAM/L-D assay (flow cytometry) after 24 h of treatment with DOX, LAP-mPEG/DOX, and LAP-cPEG/DOX.
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