Kamonrak Cheewatanakornkool

Novel pH-responsive dextrin nanogels for doxorubicin delivery to cancer cells with reduced cytotoxicity to cardiomyocytes and stem cells

The aim of this study was to develop pH-responsive dextrin nanogels (DNGs) capable of triggered intracellular DOX release at the lower pH of cancer cells. DNGs were prepared by an emulsion cross-linking method using glyoxal as cross-linker to create an acid-labile bond. A higher molecular weight of dextrin with increasing mole ratio of dextrin to glyoxal decreased the average diameter of DNGs. DNGs showed slightly negative surface charge and pH-responsive behavior. The in vitro drug release was slow at pH 7.4 and increased with decreasing pH (pH 5>6.8). The cytotoxicity of DOX-loaded DNGs in mesenchymal stem cells and cardiomyocytes was lower than that of free DOX. Moreover, DOX-loaded DNGs were efficiently internalized by tumor cells with rapid release of DOX into the nucleus. Thus, DOX-loaded DNGs were successful for intracellular targeted anti-tumor drug delivery and reducing side-effects to non-tumor cells such as cardiomyocytes and stem cells.

Enhanced anti-tumor effect of pH-responsive dextrin nanogels delivering doxorubicin on colorectal cancer

Efficacy of doxorubicin (DOX) in colorectal cancer treatment is limited by undesirable side-effects, which are partially due to nonspecific delivery DOX to the tumor target site. This study aimed to develop pH-responsive dextrin nanogels (DNGs) as anticancer drug carriers with pH-controlled drug release. DNGs prepared with formaldehyde as a cross-linker (FDNGs) exhibited smaller size, compared to that using glyoxal (GDNGs). Both DNGs showed pH-dependent drug release properties; drug release was slow at neutral pH but increased significantly in acidic medium. The cytotoxicity of empty and DOX-loaded FDNGs was lower than free DOX and GDNGs, against two commonly used colorectal cancer cells. Intracellular uptake studies indicated that the DOX-loaded FDNGs could efficiently deliver DOX into the nuclei. In vivo, DOX-loaded FDNGs substantially enhanced anti-tumor efficacy, compared to free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis, as confirmed by mice weight shifts, tumor weight, tumor volume and histological assessment. Therefore, FDNGs are promising as a potential drug delivery vehicle for colorectal cancer therapy.

Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets

Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material.

Thiolated pectin–doxorubicin conjugates: Synthesis, characterization and anticancer activity studies

In this paper, pectin was cross-linked by a coupling reaction with either thioglycolic acid or cystamine dihydrochloride to form thiolated pectins. The thiolated pectins were then coupled with doxorubicin (DOX) derivative to obtain thiolated pectin-DOX conjugates by two different methods, disulfide bond formation and disulfide bond exchange. The disulfide bond exchange method provided a simple, fast, and efficient approach for synthesis of thiolated pectin-DOX conjugates, compared to the disulfide bond formation. Characteristics, physicochemical properties, and morphology of thiolated pectins and thiolated pectin-DOX conjugates were determined. DOX content in thiolated pectin-DOX conjugates using low methoxy pectin was found to be higher than that using high methoxy pectin. The in vitro anticancer activity of thiolated pectin-DOX conjugates was significantly higher than that of free DOX, in mouse colon carcinoma and human bone osteosarcoma cells, but insignificantly different from that of free DOX, in human prostate cancer cells. Due to their promising anticancer activity in mouse colon carcinoma cells, the thiolated pectin-DOX conjugates might be suitable for building drug platform for colorectal cancer-targeted delivery of DOX.

Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment

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Comparison of In Vitro Binding of Bile Salt by Pectins from Various Sources

Binding of bile salts by dietary fiber is believed to promote their excretion and hence to reduce the serum cholesterol level in man and experimental animals. In this study, the binding efficiency of soluble pectin from various sources, i.e., apple, citrus and pomelo, was examined. Sodium deoxycholate and sodium cholate hydrate were used as a model to represent bile salt in human body. The binding efficiency was assayed by acid reaction, thin layer chromatography (TLC) and enzyme cycling method. The results demonstrated that enzyme cycling method was the most suitable for assaying the in-vitro binding of bile salts while the TLC was not very sensitive, i.e., low amount of bile salts cannot be detected by TLC. Excess pectin from binding test could also interfere the acid reaction method even though the centrifugation was used to remove the excess pectin. When the concentration of pectin was increased, the binding efficiency with sodium deoxycholate increased. However, at 1% w/w of pectin, the binding efficiency decreased. The exception is for pomelo pectin in which the binding efficiency increased when the pectin concentration increased. With sodium cholate hydrate, only slight difference in binding efficiency was observed for all types and concentrations of pectin. The results indicate that the ability to bind bile salts of pectin might be responsible for its hypocholesterolemic action observed in experimental animals and humans.

Dissolution Improvement of Itraconazole by a Nanoparticulate System Containing Lecithin-Pectin Complexes

Nanoparticulate system composing of polymeric or lipid materials have been proposed as drug carriers for improving efficacy of encapsulated drugs. Different materials, e.g. phospholipids and polysaccharides, have been proposed for the production of these systems due to their biocompatibility, biodegradability, low cost and safety. In this study, we report a novel particulate system containing lecithin-pectin complexes loaded with a lipophilic drug, itraconazole. The effect of pectin concentration on particle formation and drug dissolution was also investigated. The lecithin-pectin complexes were prepared by thin film method using soya lecithin and then hydrated with different concentration of pectin solution. The surface charge (zeta potential) and particle size of complex particles were characterized. The drug dissolution was determined by using USP dissolution apparatus. The results demonstrated that the particle size of complex particles were in nanometer range. When concentration of pectin increased, the size increased slightly while the surface charge of complex particles was less negative. The drug dissolution from complex particles containing lecithin and pectin was higher than those containing only pectin.

Redox-responsive microbeads containing thiolated pectin-doxorubicin conjugate inhibit tumor growth and metastasis: An in vitro and in vivo study

ABSTRACT The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox‐responsive microbeads containing thiolated pectin–doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract and allow redox‐triggered drug release in the colon. Morphology, particle size, drug content, and in vitro drug release behavior of the microbeads were characterized; in vitro cytotoxicity was tested on mouse colon carcinoma, human colorectal adenocarcinoma, and human bone osteosarcoma cell lines. In vivo anticancer efficacy of coated microbeads was examined in BALB/c mice with murine colon carcinoma. These coated microbeads significantly inhibited the growth of all cell lines. The in vivo study confirmed delivery of DOX to the colorectal tumor site, redox‐responsiveness, and anticancer efficacy of coated microbeads. Coated microbeads also effectively inhibited primary tumor growth and suppressed tumor metastases without gross toxicity to the non‐target tissue. No noticeable damage was found in mouse GI tissues, indicating lack of DOX toxicity. These novel coated microbeads containing thiolated pectin–DOX conjugate may be a promising vehicle for targeted clinical delivery of DOX to the colorectal cancer site by oral administration.