Sorafenib and 5-Fluorouracil Loaded Dual Drug Nanodelivery Systems for Hepatocellular Carcinoma and Colorectal Adenocarcinoma

Ruman, Umme; Buskaran, Kalaivani; Saifullah, Bullo; Pastorin, Georgia; Fakurazi, Sharida; Hussein, Mohd Zobir

doi:10.21203/rs.3.rs-152602/v1

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…This approach ensures the integrity of each drug-loaded formulation, contributing to pharmaceutical research in tailored drug delivery for anti-tuberculosis medications. The systematic synthesis lays the groundwork for further exploration and optimization, aiming for enhanced therapeutic outcomes [11].…”

Section: Synthesis Of Pyrazinamide-loaded Chitosan Nanoparticlesmentioning

confidence: 99%

Innovative Nanodelivery Systems Transform Tuberculosis Treatment with Pyrazinamide-loaded Chitosan Nanoparticles

Pooneh Kia,

Mohd Zobir Hussein,

Umme Ruman

et al. 2024

ARMNE

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Tuberculosis (TB) stands as an enduring and formidable global health challenge, necessitating innovative methodologies to optimize therapeutic outcomes. Within this context, nanotechnology emerges as a promising modality to augment TB therapy by enabling targeted drug delivery of anti-TB agents to infect cells, thereby maximizing therapeutic efficacy while mitigating adverse effects. This study focalizes on the synthesis of chitosan nanoparticles (CSNP) as a nanocarrier for the concurrent delivery of Pyrazinamide (PYR), a pivotal antibiotic in the first-line treatment of TB. The primary objective is to overcome challenges related to the limited solubility and bioavailability of these drugs, which hinder their effectiveness and pose toxicity risks. The encapsulation of PYR within CS proves advantageous, enhancing solubility, bioavailability, and targeted drug delivery. The resulting nanocarrier, denoted as CS-PYR, is prepared through ionic gelation, involving cross-linking chitosan-loaded anti-TB carriers with tripolyphosphate to achieve nanoscale dimensions. Various analytical techniques, including XRD, FTIR, TGA, TEM, FESEM, DLS, UV-vis spectroscopy, antibacterial assays, and cytotoxic MTT assays, are utilized for a comprehensive investigation. The spherical morphology of PYR-CSNP, with an average diameter of 60 to 100 nm, is confirmed by FESEM, TEM, and DLS analyses. FTIR and XRD analyses validate the successful fabrication and multifunctional properties of PYR incorporated into the CSNP matrix. The drug-loaded CSNP exhibits improved thermal stability, displaying decomposition between 200-400°C, indicating higher temperature resistance and greater weight loss compared to the CSNP carrier due to PYR inclusion. Drug release studies show sustained release behaviour, with 90-99% release in an acidic (pH 4.8) buffer solution over seven days, following a pseudo-second-order model. Moreover, the CS-PYR nanocarrier demonstrates superior efficacy against Gram-negative and Gram-positive bacteria, attributed to drug intercalation resulting in larger inhibition zones. Cytotoxicity assessments for CS-PYR indicate 80% cell viability in MRC5 cells, underscoring the nanocarrier's potential as a safe and effective TB treatment delivery system without adversely affecting normal cells. These findings position CS-PYR as a promising nanodelivery system for TB therapy, offering enhanced precision in drug delivery and safety.

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Section: Synthesis Of Pyrazinamide-loaded Chitosan Nanoparticlesmentioning

confidence: 99%

Innovative Nanodelivery Systems Transform Tuberculosis Treatment with Pyrazinamide-loaded Chitosan Nanoparticles

Pooneh Kia,

Mohd Zobir Hussein,

Umme Ruman

et al. 2024

ARMNE

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“…Passive delivery is determined by its intrinsic properties and anatomy of the tissue or cell type. Specific ligands or recognition molecules for passive medicine delivery are not required [269]. A function of the mononuclear phagocytic system (MPS) is to capture and remove foreign bodies from the circulatory system to protect the body from harmful effects.…”

Section: Delivery Systemsmentioning

confidence: 99%

The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review)

Kozlov,

Rodimova,

Kuznetsova

2023

Sovrem Tehnol Med

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Molecular diagnostics based on small non-coding RNA molecules (in particular microRNA) is a new direction in modern biomedicine and is considered a promising method for identification of a wide range of pathologies at an early stage, clinical phenotype assessment, as well as monitoring the course of the disease, evaluation of therapy efficacy and the risk of the disease recurrence. Currently, the role of microRNAs as the most important epigenetic regulator in cancer development has been proven within the studies of normal and pathogenic processes. However, currently, there are insignificant studies devoted to studying the role of microRNAs in functioning of other organs and tissues, as well as to development of possible therapeutic approaches based on microRNAs. A huge number of metabolic processes in the liver are controlled by microRNAs, which creates enormous potential for the use of microRNAs as a diagnostic marker and makes it a target for therapeutic intervention in metabolic, oncological, and even viral diseases of this organ.This review examines various aspects of biological functions of microRNAs in different types of liver cells. Both canonical and non-canonical pathways of biogenesis, epigenetic regulation mediated by microRNAs, as well as the microRNAs role in intercellular communication and the course of viral diseases are shown. The potential of microRNAs as a diagnostic marker for various liver pathologies is described, as well as therapeutic approaches and medicines based on microRNAs, which are approved for clinical use and currently being developed.

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“…Overall, the conjugation of folate to CSNPs can significantly impact their size and biological properties, and these factors should be carefully considered in the design and development of targeted drug-delivery systems [66,68,69].…”

Section: Physical and Morphology Nanoparticlesmentioning

confidence: 99%

“…Conjugating polymers with targeting ligands, such as folate, has become a popular approach for targeted drug delivery. The increased internalization of NPs through endocytosis is mostly due to the specific interaction of folate receptors overexpressed in breast cancer cells [69]. In previous studies, passive targeting based on physicochemical properties, such as size and surface charge, has been easily adjustable by adjusting the component molecules or fabrication method [57].…”

Section: In Vitro Cytotoxicitymentioning

confidence: 99%

Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated Chitosan Nanoparticles in MCF-7 Breast Cancer Cells

Herdiana,

Wathoni,

Shamsuddin

et al. 2023

Molecules

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α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer.

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Sorafenib and 5-Fluorouracil Loaded Dual Drug Nanodelivery Systems for Hepatocellular Carcinoma and Colorectal Adenocarcinoma

Cited by 6 publications

References 24 publications

Innovative Nanodelivery Systems Transform Tuberculosis Treatment with Pyrazinamide-loaded Chitosan Nanoparticles

Innovative Nanodelivery Systems Transform Tuberculosis Treatment with Pyrazinamide-loaded Chitosan Nanoparticles

The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review)

Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated Chitosan Nanoparticles in MCF-7 Breast Cancer Cells

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