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. 2023 Jan 16;7(2):167-175.
doi: 10.7150/ntno.81173. eCollection 2023.

Drug Encapsulated Lipid-Polymeric Nanohybrid as a Chemo-therapeutic Platform of Cancer

Rahul Kumar  1 , Vinish Ranjan Srivastava  1 , Supratim Mahapatra  1 , Daphika S Dkhar  1 , Rohini Kumari  1 , Kumari Prerna  1 , Vikash Kumar Dubey  1 , Pranjal Chandra  1
Affiliations

Drug Encapsulated Lipid-Polymeric Nanohybrid as a Chemo-therapeutic Platform of Cancer

Rahul Kumar et al. Nanotheranostics. .

Abstract

The focus of this research is to design a bioengineered drug delivery vehicle that is efficient in anti-cancer drug delivery in a controlled manner. The experimental work focuses on constructing a methotrexate-loaded nano lipid polymer system (MTX-NLPHS) that can transport methotrexate (MTX) in MCF-7 cell lines in a controlled manner through endocytosis via phosphatidylcholine. In this experiment, MTX is embedded with polylactic-co-glycolic acid (PLGA) in phosphatidylcholine, which acts as a liposomal framework for regulated drug delivery. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and dynamic light scattering (DLS) were utilized to characterize the developed nanohybrid system. The particle size and encapsulation efficiency of the MTX-NLPHS were found to be 198 ± 8.44 nm and 86.48 ± 0.31 %, respectively, which is suitable for biological applications. The polydispersity index (PDI) and zeta potential of the final system were found to be 0.134 ± 0.048 and -28 ± 3.50 mV, respectively. The lower value of PDI showed the homogenous nature of the particle size, whereas higher negative zeta potential prevented the system from agglomeration. An in vitro release kinetics was conducted to see the release pattern of the system, which took 250 h for 100% drug release This kind of system may carry the drug for a long time in the circulatory system and prevent the drug discharge. Other cell culture assays such as 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and reactive oxygen species (ROS) monitoring were used to see the effect of inducers on the cellular system. MTT assay showed cell toxicity of MTX-NLPHS reduced at the lower concentration of the MTX, however, toxicity increased at the higher concentration of the MTX as compared to free MTX. ROS monitoring c revealed more scavenging of ROS using MTX-NLPHS as compared to free MTX. Confocal microscopy suggested the MTX-NLPHS induced more nuclear elongation with cell shrinkage comparatively.

Keywords: MCF-7 cells; drug delivery; lipid; methotrexate; nanohybrid system; theranostics.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
The figure depicting the schematic representation of nanohybrid system formulation and its cellular internalization.
Figure 2
Figure 2
Shows the DLS pattern with size distribution (nm) for (A) MTX-NLS and, (B) MTX-NLPHS.
Figure 3
Figure 3
The SEM image of the nanohybrid system(A) MTX-NLS and (B) MTX-NLPHS.
Figure 4
Figure 4
The infrared spectrum of MTX-NLS (red curve) and MTX-NLPHS (blue curve) at the resolution of 4 cm-1.
Figure 5
Figure 5
Diffraction pattern of MTX-NLS (blue curve) and MTX-NLPHS (red curve) scanned between 2θ = 5° to 2θ = 20°.
Figure 6
Figure 6
Drug release kinetics of MTX from NLPHS (In vitro) in phosphate buffer saline for Zero-order kinetics (blue curve) and first-order kinetics (red curve) at physiological pH with a significance level of (p≤0.05*).
Figure 7
Figure 7
Cell toxicity studies on MCF-7 cells (In vitro) treated with inducers MTX and MTX-NLPHS after 48 h of incubation. Values are reported as (mean ± standard error) and significance level as p<0.05.
Figure 8
Figure 8
ROS study in MCF-7 cells (A) Untreated cells (Negative control) (B) Cells treated with H2O2 (Positive control) (C) MTX (D) MTX-NLPHS.
Figure 9
Figure 9
Study of nuclear morphology of MCF-7 cells stained with DAPI and PI dyes using confocal microscopy. Row 1 represents the untreated cells (control), Row 2 represents the cells treated with the hollow NLPHS carrier, Row 3 represents the free MTX-treated cells, and Row 4 represents the MTX-NLPHS-treated cells. Column 1 shows blue fluorescence from DAPI staining, column 2 shows red fluorescence from PI staining, and Column 3 represents the merged images.
See this image and copyright information in PMC

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