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1.
Carbohydr Polym ; 342: 122356, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39048219

ABSTRACT

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.


Subject(s)
Doxorubicin , Galactose , Mannans , Nanoconjugates , Doxorubicin/pharmacology , Doxorubicin/chemistry , Mannans/chemistry , Mannans/pharmacology , Galactose/chemistry , Galactose/analogs & derivatives , Humans , Nanoconjugates/chemistry , Hydrogen-Ion Concentration , Drug Liberation , Cell Line, Tumor , Drug Carriers/chemistry , Cell Survival/drug effects , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
2.
Int J Biol Macromol ; 185: 390-402, 2021 Aug 31.
Article in English | MEDLINE | ID: mdl-34153357

ABSTRACT

Stimulus-responsive nanoparticles stand out in studies for cancer treatment since these systems can promote a selective release of the drug in tumor tissues and cells, minimizing the effects caused by conventional chemotherapy. Dextran-graft-poly (N-isopropylacrylamide) copolymers were synthesized via Schiff base formation. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (NMR) and the analyses of dynamic light scattering (DLS) showed that the copolymers were thermal and pH dual-responsive. The chemotherapy drug doxorubicin (DOX) was conjugated to the copolymers via Schiff base formation, obtaining nanoparticles by self-assembling with size smaller than 130 nm. A higher percentage of doxorubicin was released at pH 5.0 (59.1 ± 2.1%) compared to physiological pH (34.9 ± 4.8%), confirming a pH-sensitive release profile. The in vitro cytotoxicity assay demonstrated that DOX-loaded nanoparticles can inhibit cancer cell proliferation and promote reduced cytotoxicity in non-tumor cells. The D45kP30k-DOX nanoparticles induced morphological changes in HCT-116 cells suggesting cell death and the cell uptake assay indicated that the nanoparticles can be internalized by endocytosis. Therefore, DOX-loaded nanoparticles exhibited potential as smart systems for cancer treatment.


Subject(s)
Acrylamides/chemistry , Dextrans/chemistry , Doxorubicin/pharmacology , Prodrugs/pharmacology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Doxorubicin/chemistry , HCT116 Cells , Humans , Hydrogen-Ion Concentration , Mice , Micelles , Prodrugs/chemistry , Schiff Bases/chemistry
3.
Int J Biol Macromol ; 179: 314-323, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33675833

ABSTRACT

Polysaccharide based copolymers have been the focus of several research, particularly for the development of drug delivery systems. This study reports on the preparation of nanoparticles from an amphiphilic copolymer obtained by the poly(ε-caprolactone) graft in the structure of cashew gum, via ring-opening polymerization. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. The copolymers exhibit self-organization capability in water, with critical association concentration of 42 and 50 µg mL-1. The nanoparticle hydrodynamic diameters (212 and 202 nm) revealed a decreasing trend with increasing poly(ε-caprolactone) graft percentage. Epirubicin was used as an anticancer drug model and incorporated into the nanoparticles. The encapsulation efficiency reached 50% and 5.0% drug load. Nanoparticles showed an epirubicin controlled release profile, with maximum release of 93.0 ± 4.0% in 72 h, as well as excellent biocompatibility, according to hemolysis and cytotoxicity assays.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Carriers/chemistry , Epirubicin/pharmacology , Nanoparticles/chemistry , Plant Gums/chemistry , Polyesters/chemistry , Anacardium/chemistry , Animals , Humans , MCF-7 Cells , Mice
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