Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Fong, Stephanie Sally; Foo, Yiing Yee; Saw, Wen Shang; Leo, Bey Fen; Teo, Yin Yin; Chung, Ivy; Goh, Boon Tong; Misran, Misni; Imae, Toyoko; Chang, Chia-Ching; Chung, Lip Yong; Kiew, Lik Voon

doi:10.2147/ijn.s337093

Cited by 28 publications

(13 citation statements)

References 49 publications

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“…CS as a coating material led to an increase in encapsulation efficiency of the NPs. In the literature, there are several studies claiming that CS enhances the entrapment efficiency of NP systems [ 46 – 48 ]. While CS coats the surface of the NP, it also allows for the adsorption of the drug molecules on the NP surface [ 49 ].…”

Section: Resultsmentioning

confidence: 99%

Orally administered docetaxel-loaded chitosan-decorated cationic PLGA nanoparticles for intestinal tumors: formulation, comprehensive in vitro characterization, and release kinetics

Ünal¹,

Doğan²,

Aktaş³

2022

Beilstein J. Nanotechnol.

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Intestinal cancers are the third most lethal cancers globally, beginning as polyps in the intestine and spreading with a severe metastatic tendency. Chemotherapeutic drugs used in the treatment of intestinal tumors are usually formulated for parenteral administration due to poor solubility and bioavailability problems. Pharmaceutically, clinical failure due to a drug’s wide biodistribution and non-selective toxicity is one of the major challenges of chemotherapy. In addition, parenteral drug administration in chronic diseases that require long-term drug use, such as intestinal tumors, is challenging in terms of patient compliance and poses a burden in terms of health economy. Especially in the field of chemotherapy research, oral chemotherapy is a subject that has been intensively researched in recent years, and developments in this field will provide serious breakthroughs both scientifically and socially. Development of orally applicable nanodrug formulations that can act against diseases seen in the distant region of the gastrointestinal tract (GIT), such as intestinal tumor, brings with it a series of difficulties depending on the drug and/or GIT physiology. The aim of this study is to develop an oral nanoparticle drug delivery system loaded with docetaxel (DCX) as an anticancer drug, using poly(lactic-co-glycolic acid) (PLGA) as nanoparticle material, and modified with chitosan (CS) to gain mucoadhesive properties. In this context, an innovative nanoparticle formulation that can protect orally administered DCX from GIT conditions and deliver the drug to the intestinal tumoral region by accumulating in mucus has been designed. For this purpose, DCX-PLGA nanoparticles (NPs) and CS/DCX-PLGA NPs were prepared, and their in vitro characteristics were elucidated. Nanoparticles around 250–300 nm were obtained. DCX-PLGA NPs had positive surface charge with CS coating. The formulations have the potential to deliver the encapsulated drug to the bowel according to the in vitro release studies in three different simulated GIT fluids for approximately 72 h. Mucin interaction and penetration into the artificial mucus layer were also investigated in detail, and the mucoadhesive and mucus-penetration characteristics of the formulations were examined. Furthermore, in vitro release kinetic studies of the NPs were elucidated. DCX-PLGA NPs were found to be compatible with the Weibull model, and CS/DCX-PLGA NPs were found to be compatible with the Peppas–Sahlin model. Within the scope of in vitro cytotoxicity studies, the drug-loaded NPs showed significantly higher cytotoxicity than a DCX solution on the HT-29 colon cell line, and CS/DCX-PLGA showed the highest cytotoxicity (p < 0.05). According to the permeability studies on the Caco-2 cell line, the CS/DCX-PLGA formulation increased permeability by 383% compared to free DCX (p < 0.05). In the light of all results, CS/DCX-PLGA NPs can offer a promising and innovative approach as an oral anticancer drug-loaded nanoformulation for intestinal tumors.

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Section: Resultsmentioning

confidence: 99%

Orally administered docetaxel-loaded chitosan-decorated cationic PLGA nanoparticles for intestinal tumors: formulation, comprehensive in vitro characterization, and release kinetics

Ünal¹,

Doğan²,

Aktaş³

2022

Beilstein J. Nanotechnol.

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“…The enhancement of DOX+VIN/Nio/CS cytotoxicity is due to endocytosis, which allows more niosomes to be taken up into the cells. 29,30 Also, in Figure S1C,D, the toxicities of Nio and Nio/CS formulation were determined toward the SKBR3 cell line in 48 and 72 h, respectively. There is a significant decrease in cell viability of Nio/CS compared to the Nio at all concentrations in 48 and 72 h except 0.25 μg/mL in 48 h (p < 0.05).…”

Section: Drug Release Kineticmentioning

confidence: 99%

pH-Responsive Chitosan-Adorned Niosome Nanocarriers for Co-Delivery of Drugs for Breast Cancer Therapy

Karimifard

Rezaei

Jamshidifar

et al. 2022

ACS Appl. Nano Mater.

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Breast cancer incidence has increased in recent decades. In the present study, an optimum formulation of chitosan (CS)-adorned niosome-based nanocarriers for co-delivery of doxorubicin (DOX) and vincristine (VIN) was developed for the treatment of breast cancer to reduce drug doses and overcome multidrug resistance. The three-level Box–Behnken method was utilized to optimize the particles in terms of size, polydispersity index (PDI), entrapment efficacy (EE (%)), and percent of drug release (%). The release rate of two drugs from CS-adorned nanoparticles (DOX+VIN/Nio/CS) in acidic and physiological pH is less than uncoated niosome (DOX+VIN/Nio). In addition, acidic pH increases the release rate of drugs from these formulations. The size, polydispersity index, and entrapment efficacy of nanoparticles were more stable at 4 °C compared to 25 °C. MTT assay showed that the IC50 of DOX+VIN/Nio/CS is the lowest value between all fabricated formulations. We evaluated the cancer metastasis and migration (MMP2, MMP9) and transcriptional targets for the tumor suppressor protein (Bax, Bcl2) that induces cell cycle arrest or apoptosis in response to DNA. Bax gene was highly expressed, while the Bcl2, MMP2, and MMP9 genes decreased in DOX+VIN/Nio/CS compared to control, free forms of DOX, VIN, DOX+VIN, and DOX+VIN/Nio. DOX+VIN/Nio/CS inhibited cell migration and increased apoptosis, cell uptake, and endocytosis in human SKBR3 breast cancer cells compared to DOX, VIN, DOX+VIN. These in vitro data are promising to treat breast cancer with advanced pH-responsive drug release nanoformulations.

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“…In addition, chitosan nanoparticles have already been shown to be excellent inhibitors of bacteria, both Escherichia coli and Staphylococcus aureus [ 172 ]. Recent findings include the use of chitosan in the preparation of nanocarriers to enhance the antimetastatic properties of the entrapped drug in vitro and in vivo [ 173 ].…”

Section: Animal-based Biopolymeric Nanoparticles Used For Healthcare ...mentioning

confidence: 99%

Sustainable Biodegradable Biopolymer-Based Nanoparticles for Healthcare Applications

Kučuk

Primožič

Knez

et al. 2023

IJMS

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Biopolymeric nanoparticles are gaining importance as nanocarriers for various biomedical applications, enabling long-term and controlled release at the target site. Since they are promising delivery systems for various therapeutic agents and offer advantageous properties such as biodegradability, biocompatibility, non-toxicity, and stability compared to various toxic metal nanoparticles, we decided to provide an overview on this topic. Therefore, the review focuses on the use of biopolymeric nanoparticles of animal, plant, algal, fungal, and bacterial origin as a sustainable material for potential use as drug delivery systems. A particular focus is on the encapsulation of many different therapeutic agents categorized as bioactive compounds, drugs, antibiotics, and other antimicrobial agents, extracts, and essential oils into protein- and polysaccharide-based nanocarriers. These show promising benefits for human health, especially for successful antimicrobial and anticancer activity. The review article, divided into protein-based and polysaccharide-based biopolymeric nanoparticles and further according to the origin of the biopolymer, enables the reader to select the appropriate biopolymeric nanoparticles more easily for the incorporation of the desired component. The latest research results from the last five years in the field of the successful production of biopolymeric nanoparticles loaded with various therapeutic agents for healthcare applications are included in this review.

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Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Cited by 28 publications

References 49 publications

Orally administered docetaxel-loaded chitosan-decorated cationic PLGA nanoparticles for intestinal tumors: formulation, comprehensive in vitro characterization, and release kinetics

Orally administered docetaxel-loaded chitosan-decorated cationic PLGA nanoparticles for intestinal tumors: formulation, comprehensive in vitro characterization, and release kinetics

pH-Responsive Chitosan-Adorned Niosome Nanocarriers for Co-Delivery of Drugs for Breast Cancer Therapy

Sustainable Biodegradable Biopolymer-Based Nanoparticles for Healthcare Applications

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