Potential Oral Anticancer Therapeutic Agents of Hexahydrocurcumin-Encapsulated Chitosan Nanoparticles against MDA-MB-231 Breast Cancer Cells

Hexahydrocurcumin-encapsulated chitosan nanoparticles (HHC-CS-NPs) were formulated by oil-in-water emulsification and ionotropic gelation and optimized using the Box–Behnken design. The particle size, zeta potential, and encapsulation efficiency of the optimized HHC-CS-NPs were 256 ± 14 nm, 27.3 ± 0.7 mV, and 90.6 ± 1.7%, respectively. The TEM analysis showed a spherical shape and a dense structure with a narrow size distribution. The FT-IR analysis indicated no chemical interaction between the excipients and the drugs in the nanoparticles, but the existence of the drugs was molecularly dispersed in the nanoparticle matrices. The drug release profile showed a preliminary burst release followed by a sustained release under simulated gastrointestinal (GI) and physiological conditions. A stability study suggested that the HHC-CS-NPs were stable under UV light, simulated GI, and body fluids. The in vitro bioaccessibility and bioavailability of the HHC-CS-NPs were 2.2 and 6.1 times higher than those of the HHC solution, respectively. The in vitro evaluation of the antioxidant, anti-inflammatory, and cytotoxic effects of the optimized HHC-CS-NPs demonstrated that the CS-NPs significantly improved the biological activities of HHC in radical scavenging, hemolysis protection activity, anti-protein denaturation, and cytotoxicity against MDA-MB-231 breast cancer cells. Western blot analysis showed that the apoptotic protein expression of Bax, cytochrome C, caspase-3, and caspase-9, were significantly up-regulated, whereas the anti-apoptotic protein Bcl-2 expression was down-regulated in the HHC-CS-NP-treated cells. Our findings suggest that the optimized HHC-CS-NPs can be further developed as an efficient oral treatment for breast cancer

Synergistic Effects of Photo-Irradiation and Curcumin-Chitosan/Alginate Nanoparticles on Tumor Necrosis Factor-Alpha-Induced Psoriasis-Like Proliferation of Keratinocytes

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of the epidermal cells and is clinically presented as thick, bright red to pink plaques with a silvery scale. Photodynamic therapy (PDT) using visible light has become of increasing interest in the treatment of inflammatory skin diseases. In this study, we demonstrate that a combination of curcumin-loaded chitosan/alginate nanoparticles (Cur-CS/Alg NPs) and blue light emitting diodes (LED) light irradiation effectively suppressed the hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced cultured human kerlatinocyte (HaCaT) cells. The Cur-CS/Alg NPs were fabricated by emulsification of curcumin in aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan using an optimized formulation derived from a Box-Behnken design. The fabricated Cur-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The surrogate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, to measure the relative number of viable cells, showed that the CS/Alg NPs were nontoxic to normal HaCaT cells, while 0.05 µg/mL and 0.1 µg/mL of free curcumin and Cur-CS/Alg NPs inhibited the hyperproliferation of HaCaT cells induced by TNF-α. However, the Cur-CS/Alg NPs demonstrated a stronger effect than the free curcumin, especially when combined with blue light irradiation (10 J/cm2) from an LED-based illumination device. Therefore, the Cur-CS/Alg NPs with blue LED light could be potentially developed into an effective PDT system for the treatment of psoriasis

Potential Oral Anticancer Therapeutic Agents of Hexahydrocurcumin-Encapsulated Chitosan Nanoparticles against MDA-MB-231 Breast Cancer Cells

Hexahydrocurcumin-encapsulated chitosan nanoparticles (HHC-CS-NPs) were formulated by oil-in-water emulsification and ionotropic gelation and optimized using the Box–Behnken design. The particle size, zeta potential, and encapsulation efficiency of the optimized HHC-CS-NPs were 256 ± 14 nm, 27.3 ± 0.7 mV, and 90.6 ± 1.7%, respectively. The TEM analysis showed a spherical shape and a dense structure with a narrow size distribution. The FT-IR analysis indicated no chemical interaction between the excipients and the drugs in the nanoparticles, but the existence of the drugs was molecularly dispersed in the nanoparticle matrices. The drug release profile showed a preliminary burst release followed by a sustained release under simulated gastrointestinal (GI) and physiological conditions. A stability study suggested that the HHC-CS-NPs were stable under UV light, simulated GI, and body fluids. The in vitro bioaccessibility and bioavailability of the HHC-CS-NPs were 2.2 and 6.1 times higher than those of the HHC solution, respectively. The in vitro evaluation of the antioxidant, anti-inflammatory, and cytotoxic effects of the optimized HHC-CS-NPs demonstrated that the CS-NPs significantly improved the biological activities of HHC in radical scavenging, hemolysis protection activity, anti-protein denaturation, and cytotoxicity against MDA-MB-231 breast cancer cells. Western blot analysis showed that the apoptotic protein expression of Bax, cytochrome C, caspase-3, and caspase-9, were significantly up-regulated, whereas the anti-apoptotic protein Bcl-2 expression was down-regulated in the HHC-CS-NP-treated cells. Our findings suggest that the optimized HHC-CS-NPs can be further developed as an efficient oral treatment for breast cancer

Polyethylene Glycol-Chitosan Oligosaccharide-Coated Superparamagnetic Iron Oxide Nanoparticles: A Novel Drug Delivery System for Curcumin Diglutaric Acid

Curcumin diglutaric acid-loaded polyethylene glycol-chitosan oligosaccharide-coated superparamagnetic iron oxide nanoparticles (CG-PEG-CSO-SPIONs) were fabricated by co-precipitation and optimized using a Box–Behnken statistical design in order to achieve the minimum size, optimal zeta potential (≥ ±20 mV), and maximum loading efficiency and capacity. The results demonstrated that CG-PEG-CSO-SPIONs prepared under the optimal condition were almost spherical in shape with a smooth surface, a diameter of 130 nm, zeta potential of 30.6 mV, loading efficiency of 83.3%, and loading capacity of 8.3%. The vibrating sample magnetometer results of the optimized CG-PEG-CSO-SPIONs showed a superparamagnetic behavior. Fourier transform infrared spectroscopy and X-ray diffraction analyses indicated that the CG physically interacted with PEG-CSO-SPIONs. In addition, the CG-PEG-CSO-SPIONs could be stored dry for up to 12 weeks or in aqueous solution for up to 4 days at either 4 °C or 25 °C with no loss of stability. The CG-PEG-CSO-SPIONs exhibited a sustained release profile up to 72 h under simulated physiological (pH 7.4) and tumor extracellular (pH 5.5) environments. Furthermore, the CG-PEG-CSO-SPIONs showed little non-specific protein binding in the simulated physiological environment. The CG-PEG-CSO-SPIONs enhanced the cellular uptake and cytotoxicity of CG against human colorectal adenocarcinoma HT-29 cells compared to free CG, and more CG was delivered to the cells after applying an external magnetic field. The overall results suggest that PEG-CSO-SPIONs have potential to be used as a novel drug delivery system for CG

Fabrication of Curcumin Diethyl γ-Aminobutyrate-Loaded Chitosan-Coated Magnetic Nanocarriers for Improvement of Cytotoxicity against Breast Cancer Cells

This study shows the effectiveness of magnetic-guide targeting in the delivery of curcumin diethyl γ-aminobutyrate (CUR-2GE), a prodrug of curcumin (CUR) previously synthesized to overcome unfavorable physicochemical properties of CUR. In this study, chitosan (Ch)-coated iron oxide nanoparticles (Ch-IONPs) were fabricated and optimized using Box–Behnken design-based response surface methodology for delivery of CUR-2GE. Ch was used as a coating material on the nanoparticle surface to avoid aggregation. The optimized condition for preparing Ch-IONPs consisted of using 4 mg Ch fabricated at pH 11 under a reaction temperature of 85 °C. The optimized Ch-IONPs were successfully loaded with CUR-2GE with sufficient loading capacity (1.72 ± 0.01%) and encapsulation efficiency (94.9 ± 0.8%). The obtained CUR-2GE-loaded Ch-IONPs (CUR-2GE-Ch-IONPs) exhibited desirable characteristics including a particle size of less than 50 nm based on TEM images, superparamagnetic property, highly crystalline IONP core, sufficient stability, and sustained-release profile. In the presence of permanent magnets, CUR-2GE-Ch-IONPs significantly increased cellular uptake and cytotoxicity toward MDA-MB-231 with a 12-fold increase in potency compared to free CUR-2GE, indicating the potential of magnetic-field assisted delivery of CUR-2GE-Ch-IONPs for the treatment of triple-negative breast cancer

Folic Acid-Grafted Chitosan-Alginate Nanocapsules as Effective Targeted Nanocarriers for Delivery of Turmeric Oil for Breast Cancer Therapy

Folate receptors (FRs) highly expressed in breast cancers can be used as a recognized marker for preventing off-target delivery of chemotherapeutics. In this study, folic acid (FA)-grafted chitosan-alginate nanocapsules (CS-Alg-NCs) loaded with turmeric oil (TO) were developed for breast cancer targeting. CS was successfully conjugated with FA via an amide bond with a degree of substitution at 12.86%. The TO-loaded FA-grafted CS-Alg-NCs (TO-FA-CS-Alg-NCs) optimized by Box-Behnken design using response surface methodology had satisfactory characteristics with homogenous particle size (189 nm) and sufficient encapsulation efficiency and loading capacity (35.9% and 1.82%, respectively). In vitro release study of the optimized TO-FA-CS-Alg-NCs showed a sustained TO release following the Korsmeyer-Peppas model with a Fickian diffusion mechanism at pH 5.5 and 7.4. The TO-FA-CS-Alg-NCs showed lower IC50 than ungrafted TO-CS-Alg-NCs and unencapsulated TO against MDA-MB-231 and MCF-7 breast cancer cells, suggesting that FA-CS-Alg-NCs can improve anticancer activity of TO through its active targeting to the high FRs expressing breast cancers