Applications of nanoparticles in drug delivery system and in targeted breast cancer treatment

การประยุกต์ใช้อนุภาคนาโนในการนำส่งยา และในการรักษาโรคมะเร็งเต้านมแบบมุ่งเป้า

Name: Tinnabhop Santadkha

keyword: Curcumin

; Drug release

; Anticancer drug

; Superparamagnetic nanoparticles

; Gene therapy

; Mcl-1 siRNA

; Survivin siRNA

; Breast cancer

; Prime-fect

; Trans-booster

Abstract: This research focused on nanotechnology applications in drug release from prepared iron oxide nanoparticles and combinatorial (small interfering RNA) siRNA-based nanocarriers to breast cancer cells in vitro and in vivo. The purpose of kinetic analysis of drug release from curcumin loaded Pluronic F127-Oleic acid (OA)-Fe3O4 nanoparticles was to develop diffusion and kinetic modeling of its in vitro drug release process. The prepared superparamagnetic nanoparticles by co-precipitation technique were characterized by the average size, size distribution, crystallinity, colloidal stability and magnetic property. The release of curcumin was triggered by an acidic environment in pH 5.0 of phosphate buffer saline. Release data of various curcumin loading (15, 25 and 30 ppm) were fitted using non-linear first order, second order, Higuchi and Korsmeyer-Peppas model. All the curcumin release mechanism followed Korsmeyer-Peppas model with n values less than 0.45 indicating the Fickian diffusion of curcumin from the prepared nanomicelles. The dynamic of controlled drug release of dilute curcumin loading was well described by a combination of diffusion and first-order release rate. The corresponding diffusion coefficient and kinetic rate were 9.1 × 10-7 cm2·min-1 and 6.51 × 10-7 min-1, which were used as controlled release to achieve the desired curcumin constant release rate in the delivery system. This study was extended beyond drug delivery into development of targeted breast cancer therapy by co-delivery of Mcl-1 and survivin siRNA. This research was aimed at investigating the influence of commercial transfection reagents (Prime-Fect, Leu-Fect A, and Leu-Fect C) complexed with different siRNAs (CDC20, HSP90, Mcl-1 and survivin) in MDA-MB-436 breast cancer cells and the impact of incorporating an anionic additive, Trans-Booster, into siRNA formulations for improving in vitro gene silencing and delivery efficiency. Gene silencing was quantitatively analyzed by real-time RT-PCR while cell proliferation and siRNA uptake were evaluated by the MTT assay and flow cytometry, respectively. Amongst the investigated siRNAs and transfection reagents, Mcl-1/Prime-Fect complexes showed the highest inhibition of cell viability and the most effective siRNA delivery. The effect of various formulations on transfection efficiency showed that the additive with 1:1 ratio with siRNA was optimal achieving the lowest cell viability compared to untreated cells and negative control siRNA treatment (p < 0.05). Furthermore, the combination of Mcl-1 and survivin siRNA suppressed the growth of MDA-MB-436 cells more effectively than treatment with the single siRNAs and resulted in cell viability as low as ~ 20% compared to non-treated cells. This aligned well with the induction of apoptosis as analyzed by flow cytometry, which revealed higher apoptotic cells with the combination treatment group. We conclude that commercial transfection reagents formulated with Mcl-1/Survivin siRNA combination could serve as a potent anti-proliferation agent in the treatment of breast cancers

Thammasat University. Thammasat University Library

Address: BANGKOK

Email: preserv@tu.ac.th

Name: Wanwisa Skolpap

Role: advisor

Created: 2022

Modified: 2024-02-16

Issued: 2024-02-16

วิทยานิพนธ์/Thesis

application/pdf

DOI: 10.14457/TU.the.2022.1317

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degree

Descipline: Engineering

Grantor: Thammasat University

©copyrights Thammasat University

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