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1.
Crit Rev Food Sci Nutr ; 63(29): 9731-9751, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35522080

RESUMEN

Curcumin (CUR) is a natural hydrophobic compound, which is available in turmeric rhizome. It has several bioactivities including antioxidant, anti-obesity, anti-diabetic, cardioprotective, anti-inflammatory, antimicrobial, anticancer, and other activities. Despite its medical and biological benefits, it is using in limitations because of its hydrophobicity and sensitivity. These unfavorable conditions further reduced the bioavailability (BA) and biological efficacy of CUR. This review summarizes the stability and BA of free- and encapsulated-CUR, as well as comprehensively discusses the potential biological activity of CUR-loaded various micro-/nano-encapsulation systems. The stability and BA of CUR can be improved via loading in different encapsulation systems, including nanoemulsions, liposomes, niosomes, biopolymer-based nanoparticles, nano-hydrogel, and others. Biopolymer-based nanoparticles (especially poly lactic-co-glycolic acid (PLGA), zein, and chitosan) and nano-gels are the best carriers for encapsulating and delivering CUR. Both delivery systems are suitable because of their excellent functional properties such as high encapsulation efficiency, well-stability against unfavorable conditions, and can be coated using other encapsulation systems. Based on available evidences, encapsulated-CUR exerted greater biological activities especially anticancer (breast cancer), antioxidant, antidiabetic, and neuroprotective effects.


Asunto(s)
Curcumina , Nanopartículas , Humanos , Curcumina/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Portadores de Fármacos/química , Antioxidantes/farmacología , Nanopartículas/química , Liposomas , Biopolímeros , Tamaño de la Partícula
2.
Cell Biol Int ; 47(4): 808-822, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36640423

RESUMEN

Carbon quantum dots (CQDs) derived from natural sources have obtained potential interest in biomedical imaging and therapy because of their excellent biocompatibility properties, which include water solubility, simple synthesis and low cytotoxicity. Here the cytotoxicity of ethylene-diamine doped carbon quantum dots (N-CQDs) delivered to breast cancer MCF-7 cells was investigated. Folic acid was used to raise folate recognition and increase FA-NCQD accumulation in the cells, then apoptosis was assayed using nuclear fragmentation, acridine orange labeling, fluorescence imaging, flow cytometry, and caspase 3 expression. The data show that functionalization of these CQDs, derived from a natural source, have potential application in eliminating cancer cells, as shown here for the invasive breast cancer cells, MCF-7. This nano-delivery system provides a novel target therapy possibility therapeutic approach for cancer cells.


Asunto(s)
Neoplasias de la Mama , Puntos Cuánticos , Femenino , Humanos , Apoptosis , Carbono , Análisis Costo-Beneficio , Células MCF-7
3.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36834960

RESUMEN

Bevacizumab (Bev) a humanized monoclonal antibody that fights vascular endothelial growth factor A (VEGF-A). It was the first specifically considered angiogenesis inhibitor and it has now become the normative first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the current study, polyphenolic compounds were isolated from bee pollen (PCIBP) and encapsulated (EPCIBP) inside moieties of hybrid peptide-protein hydrogel nanoparticles in which bovine serum albumin (BSA) was combined with protamine-free sulfate and targeted with folic acid (FA). The apoptotic effects of PCIBP and its encapsulation (EPCIBP) were further investigated using A549 and MCF-7 cell lines, providing significant upregulation of Bax and caspase 3 genes and downregulation of Bcl2, HRAS, and MAPK as well. This effect was synergistically improved in combination with Bev. Our findings may contribute to the use of EPCIBP simultaneously with chemotherapy to strengthen the effectiveness and minimize the required dose.


Asunto(s)
Antineoplásicos , Bevacizumab , Productos Biológicos , Carcinoma de Pulmón de Células no Pequeñas , Hidrogeles , Animales , Humanos , Células A549/efectos de los fármacos , Células A549/metabolismo , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Abejas/química , Abejas/metabolismo , Bevacizumab/uso terapéutico , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Hidrogeles/química , Hidrogeles/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Células MCF-7/efectos de los fármacos , Células MCF-7/metabolismo , Nanopartículas/química , Nanopartículas/uso terapéutico , Polen/química , Polen/metabolismo , Factor A de Crecimiento Endotelial Vascular/uso terapéutico
4.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36362075

RESUMEN

Non-small cell lung cancer (NSCLC) is an important sub-type of lung cancer associated with poor diagnosis and therapy. Innovative multi-functional systems are urgently needed to overcome the invasiveness of NSCLC. Carbon quantum dots (CQDs) derived from natural sources have received interest for their potential in medical bio-imaging due to their unique properties, which are characterized by their water solubility, biocompatibility, simple synthesis, and low cytotoxicity. In the current study, ethylene-diamine doped CQDs enhanced their cytotoxicity (98 ± 0.4%, 97 ± 0.38%, 95.8 ± 0.15%, 86 ± 0.15%, 12.5 ± 0.14%) compared to CQDs alone (99 ± 0.2%, 98 ± 1.7%, 96 ± 0.8%, 93 ± 0.38%, 91 ± 1.3%) at serial concentrations (0.1, 1, 10, 100, 1000 µg/mL). In order to increase their location in a specific tumor site, folic acid was used to raise their functional folate recognition. The apoptotic feature of A549 lung cells exposed to N-CQDs and FA-NCQDs was characterized by a light orange-red color under fluorescence microscopy. Additionally, much nuclear fragmentation and condensation were seen. Flow cytometry results showed that the percentage of cells in late apoptosis and necrosis increased significantly in treated cells to (19.7 ± 0.03%), (27.6 ± 0.06%) compared to untreated cells (4.6 ± 0.02%), (3.5 ± 0.02%), respectively. Additionally, cell cycle arrest showed a strong reduction in cell numbers in the S phase (14 ± 0.9%) compared to untreated cells (29 ± 0.5%). Caspase-3 levels were increased significantly in A549 exposed to N-CQDs (2.67 ± 0.2 ng/mL) and FA-NCQDs (3.43 ± 0.05 ng/mL) compared to untreated cells (0.34 ± 0.04 ng/mL). The functionalization of CQDs derived from natural sources has proven their potential application to fight off non-small lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Puntos Cuánticos , Humanos , Carbono , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Microscopía Fluorescente , Ácido Fólico
5.
J Mater Sci Mater Med ; 28(8): 120, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28685231

RESUMEN

TGFß1 pathway antagonists have been considered promising therapies to attenuate TGFß downstream signals in cancer cells. Inhibiting peptides, as P-17 in this study, are bound to either TGFß1 or its receptors, blocking signal transduction. However, for efficient use of these TGFß1antagonist as target therapeutic tools, improvement in their delivery is required. Here, a plasmid carrying specific shDNA (SHT-DNA), small interfering RNA (siRNA), and the peptide (P-17) were loaded separately into folic acid (FA)-functionalized nano-carriers made of Bovine Serum Albumin (BSA). The two building blocks of the carrier, (BSA and FA) were used because of the high affinity of albumin for liver and for the overexpression of folate receptors on the membrane of hepatocellular carcinoma cells. The empty and the encapsulated carriers were thoroughly investigated to characterize their structure, to evaluate the colloidal stability and the surface functionalization. The entrapment of SHT-DNA, siRNA and P-17, respectively, was demonstrated by morphological and quantitative analysis. Finally, cellular studies were performed to assess the targeting efficiency of the hybrid carriers. These vectors were used because of the high affinity of albumin for liver and for the overexpression of folate receptors on the membrane hepatocellular carcinoma cells. The empty and the encapsulated carriers were thoroughly investigated to characterize their structure, to evaluate the colloidal stability and the surface functionalization. The entrapment of SHT-DNA, siRNA and P-17, respectively, was demonstrated by morphological and quantitative analysis. A novel fabrication of Hybrid Polymeric-Protein Nano-Carriers (HPPNC) for delivering TGF ß1 inhibitors to HCC cells has been developed. SHT-DNA, siRNA and P-17 have been successfully encapsulated. TGF ß1 inhibitors-loaded HPPNC were efficiently uptaken by HLF cells.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Portadores de Fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Polímeros/química , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Animales , Bovinos , Coloides/química , Sistemas de Liberación de Medicamentos , Receptores de Folato Anclados a GPI/metabolismo , Ácido Fólico/química , Humanos , Microscopía de Fuerza Atómica , Microscopía Fluorescente , Péptidos/química , ARN Interferente Pequeño/metabolismo , Albúmina Sérica Bovina , Espectroscopía Infrarroja por Transformada de Fourier
6.
Int J Biol Macromol ; 260(Pt 1): 129338, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38232870

RESUMEN

BACKGROUND: Cancer is a popular disease among many others that can threaten human life. This is not only because of its invasiveness but also because of its resistance and the highly effective cost of its treatments. Propolis is rich in natural bioactive and polyphenolic compounds that have proven their strong effect on cancer cells such as MCF-7 and A549 cell lines. METHODS: Propolis extract was immobilized into the bovine serum albumin (BSA) conjugated to folic acid (FA), to increase control of its delivery and to strengthen its cellular uptake. RESULTS: The growth of MCF-7 was significantly decreased by propolis extract and BSA-propolis NPs after their incubation for 48 and 72 h by (54 ± 0.01 %, and 45 ± 0.005 %, P ≤ 0.001) and (20 ± 0.01 % and 10 ± 0.005 %, P ≤ 0.0001), respectively. Similarly, there is a significant inhibition in the growth of A549 obtained after their incubation with (propolis extract and albumin-propolis NPs) for 72 h (15 ± 0.03 % and 5 ± 0.01 %, P ≤ 0.00001). Propolis extract and BSA-propolis NPs exhibited a greater effect on protein expression of MCF-7 and A549, showing significant modulation of caspase-3, cyclin D1, and light chain 3 (LC3II). The result was supported by nuclear fragmentations and activation of acidic/neutral autophagosomes in acridine orange/ethidium bromide (AO/EB) and 4',6-diamidino-2-phenylindole (DAPI) nuclear stains. According to this study, the expression of phospho-GSK3ß (Ser9) (p < 0.001) increased significantly in MCF-7 and A549 cells after their exposure to propolis extract and BSA-propolis NPs. CONCLUSION: Results support the potency application of propolis and its encapsulation as an alternative therapeutic agent for cancer treatments instead of chemotherapies because of its action on multi-signaling pathways.


Asunto(s)
Neoplasias Pulmonares , Nanopartículas , Própolis , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Própolis/farmacología , Línea Celular Tumoral , Albúmina Sérica Bovina
7.
Biology (Basel) ; 13(7)2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39056682

RESUMEN

Fatty liver injury is a prevalent condition in most farmed fish, yet the molecular mechanisms underpinning this pathology remain largely elusive. A comprehensive feeding trial spanning eight weeks was conducted to discern the potential of dietary chitosan in mitigating the deleterious effects of a high-fat diet (HFD) while concurrently exploring the underlying mechanism. Growth performance, haemato-biochemical capacity, antioxidant capacity, apoptotic/anti-apoptotic gene expression, inflammatory gene expression, and histopathological changes in the liver, kidney, and intestine were meticulously assessed in Nile tilapia. Six experimental diets were formulated with varying concentrations of chitosan. The first three groups were administered a diet comprising 6% fat with chitosan concentrations of 0%, 5%, and 10% and were designated as F6Ch0, F6Ch5, and F6Ch10, respectively. Conversely, the fourth, fifth, and sixth groups were fed a diet containing 12% fat with chitosan concentrations of 0%, 5%, and 10%, respectively, for 60 days and were termed F12Ch0, F12Ch5, and F12Ch10. The results showed that fish fed an HFD demonstrated enhanced growth rates and a significant accumulation of fat in the perivisceral tissue, accompanied by markedly elevated serum hepatic injury biomarkers and serum lipid levels, along with upregulation of pro-apoptotic and inflammatory markers. In stark contrast, the expression levels of nrf2, sod, gpx, and bcl-2 were notably decreased when compared with the control normal fat group. These observations were accompanied by marked diffuse hepatic steatosis, diffuse tubular damage, and shortened intestinal villi. Intriguingly, chitosan supplementation effectively mitigated the aforementioned findings and alleviated intestinal injury by upregulating the expression of tight junction-related genes. It could be concluded that dietary chitosan alleviates the adverse impacts of an HFD on the liver, kidney, and intestine by modulating the impaired antioxidant defense system, inflammation, and apoptosis through the variation in nrf2 and cox2 signaling pathways.

8.
Acta Histochem ; 125(4): 152032, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37119607

RESUMEN

The migratory process is a highly organized, differentiated, and polarized stage by which many signaling pathways are regulated to control cell migration. Since the significant evidence of migrating cells is the reorganization of the cytoskeleton. In the recent study, the cell migration model was assessed on the fact that any disruption obtained in the cellular monolayer confluent, may cause stimulation for surrounding cells to migrate. We attempt to demonstrate the morphological alterations associated with these migrating cells. In this case, sterilized 1 N NaOH (1 µl) was used as alkaline burnt. It leads to scratching the monolayer of hepatocellular carcinoma (HLF cell line) allowing cells to lose their connection. Scanning electron microscopy (SEM), fluorescence microscopy, light inverted microscopy, and dark field were used for discovering the morphological alterations associated with migrating cancer cells. The findings show that cells exhibited distinctive alterations including a polarizing stage, accumulation of the actin nodules in front of the nucleus, and protrusions. Nuclei appeared as lobulated shapes during migration. Lamellipodia and uropod were extended as well. Additionally, TGFß1 proved its expression in HLF and SNU449 after their stimulation. It is demonstrated that hepatocellular carcinoma cells can migrate after their stimulation and there is a caution against the indiscriminate application of alkalinizing drug therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Actinas/metabolismo , Movimiento Celular , Línea Celular Tumoral , Concentración de Iones de Hidrógeno
9.
Int J Biol Macromol ; 245: 125572, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37385311

RESUMEN

The objective of this study is to activate autophagy in hepatocellular carcinoma for the enhancement of its cellular degradation. Liposomes incorporated chitosan in the core used to improve the stability of lecithin and increase the niacin loading efficiency. Additionally, curcumin as a hydrophobic molecule entrapped into liposomal layers and used as a face layer to minimize the release of niacin in physiological pH 7.4. Folic acid-conjugated chitosan was used to facilitate the delivery of liposomes into a specific location of cancer cells. TEM, UV Visible spectrophotometer, and FTIR confirmed the successful liposomal formation and good encapsulation efficiency. Based on the cellular proliferation of HePG2, the results revealed that there was a significant inhibition of growth rate of HePG2 after 48 h of incubation at a concentration of 100 µg/mL by 91 % ± 1 %, P ≤ 0.002 (pure niacin), 55 % ± 3 %, P ≤ 0.001 (pure curcumin), 83 % ± 1.5 %, P ≤ 0.001 (niacin NPs), and 51 % ± 1.5 % P ≤ 0.0001 (curcumin-niacin NPs) of relative to the control. Increasingly, The expression of mRNA of mTOR was significantly increased by 0.72 ± 0.08 P ≤ 0.001, 1 ± 0.1, 0. P ≤ 0.001, 5 ± 0.07 P ≤ 0.01, and 1.3 ± 0.02 P ≤ 0.001 folds) in pure niacin, pure curcumin, niacin NPs and curcumin -niacin NPs, respectively, relative to the control with an expression of 0.3 ± 0.08. Additionally, the expression of p62 mRNA was significantly increased by 0.92 ± 0.07 P ≤ 0.05, 1.7 ± 0.07 P ≤ 0.0001, 0.72 ± 0.08 P ≤ 0.5, and 2.1 ± 0.1 P ≤ 0.0001 folds relative to that of the control with an expression of 0.72 ± 0.08. The results highlight the efficient therapies of biomaterials derived from natural sources that can be used in cancer therapies instead of traditional chemotherapies.


Asunto(s)
Carcinoma Hepatocelular , Quitosano , Curcumina , Neoplasias Hepáticas , Nanopartículas , Niacina , Humanos , Liposomas , Curcumina/farmacología , Curcumina/química , Carcinoma Hepatocelular/tratamiento farmacológico , Quitosano/química , Niacina/farmacología , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Portadores de Fármacos/química , Autofagia , Nanopartículas/química , Tamaño de la Partícula
10.
Int J Biol Macromol ; 198: 101-110, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-34968533

RESUMEN

Respiratory infected by COVID-19 represents a major global health problem at moment even after recovery from virus corona. Since, the lung lesions for infected patients are still sufferings from acute respiratory distress syndrome including alveolar septal edema, pneumonia, hyperplasia, and hyaline membranes Therefore, there is an urgent need to identify additional candidates having ability to overcome inflammatory process and can enhance efficacy in the treatment of COVID-19. The polypenolic extracts were integrated into moeties of bovine serum albumin (BSA) and then were coated by chitosan as a mucoadhesion polymer. The results of interleukin-6, and c-reactive protein showed significant reduction in group treated by Encap. SIL + CUR (64 ± 0.8 Pg/µL & 6 ± 0.5 µg/µL) compared to group treated by Cham. + CUR (102 ± 0.8 Pg/µL & 7 ± 0.5 µg/µL) respectively and free capsules (with no any drug inside) (148 ± 0.6 Pg/µL & 10 ± 0.6 µg/µL) respectively. Histopathology profile was improved completely. Additionally, encapsulating silymarin showed anti-viral activity in vitro COVID-19 experiment. It can be summarized that muco-inhalable delivery system (MIDS) loaded by silymarin can be used to overcome inflammation induced by oleic acid and to overcome COVID-19.


Asunto(s)
Antiinflamatorios/farmacología , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Curcumina/farmacología , Lesión Pulmonar/tratamiento farmacológico , Nanopartículas/química , Silimarina/farmacología , Administración por Inhalación , Animales , Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Proteína C-Reactiva/metabolismo , Manzanilla/química , Quitosano/química , Chlorocebus aethiops , Curcumina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Flavonoides/análisis , Flavonoides/química , Interleucina-6/metabolismo , Lesión Pulmonar/sangre , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/patología , Masculino , Ratones , Silybum marianum/química , Nanopartículas/administración & dosificación , Ácido Oléico/toxicidad , Silimarina/administración & dosificación , Células Vero , Ensayo de Placa Viral
11.
Pharmaceutics ; 14(6)2022 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-35745733

RESUMEN

Apigenin (Ap) is one of the most important natural flavonoids that has potent anticancer activity. This study was designed, for the first time, to load Ap into chitosan to improve its hydrophobicity and then it was coated with albumin-folic acid to increase its stability and bioavailability and to target cancer cells. The newly developed encapsulated Ap (Ap-CH-BSA-FANPs) was characterized and tested in vitro. The zeta potential of -17.0 mV was within the recommended range (-30 mV to +30 mV), indicating that encapsulated apigenin would not quickly settle and would be suspended. The in vitro results proved the great anticancer activity of the encapsulated apigenin on HePG-2 cells compared to pure Ap. The treated HePG-2 cells with Ap-CH-BSA-FANPs demonstrated the induction of apoptosis by increasing p53 gene expression, arresting the cell cycle, increasing caspase-9 levels, and decreasing both the MMP9 gene and Bcl-2 protein expression levels. Moreover, the higher antioxidant activity of the encapsulated apigenin treatment was evident through increasing SOD levels and decreasing the CAT concentration. In conclusion, the Ap-CH-BSA-FANPs were easy to produce with low coast, continued drug release, good loading capacity, high solubility in physiological pH, and were more stable than the formerly Ap-loaded liposomes or PLGA. Moreover, Ap-CH-BSA-FANPs may be a promising chemotherapeutic agent in the treatment of HCC.

12.
Int J Biol Macromol ; 206: 467-480, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35202638

RESUMEN

Lung cancer is the most common cause of cancer death worldwide. Thereby, new treatment strategies as targeting nano-therapy present promising possibilities to control the aggressiveness of lung cancer. Dual CD44 and folate receptors targetable nanocapsule based on folic-polyethylene glycol-hyaluronic (FA-PEG-HA) were fabricated to improve the therapeutic activity of 4-Methylumbelliferone (4-MU) toward lung cancer. In this study, we fabricate 4-MU Nps as a hybrid polymeric (protamine) protein (albumin) nanocapsule, then functionalized by targeting layer to form 4-MU@FA-PEG-HA Nps with encapsulation efficacy 96.15%. The in vitro study of free 4-MU, 4-MU Nps and 4-MU@FA-PEG-HA Nps on A549 lung cancer cells reveal that the 4-MU Nps and 4-MU@FA-PEG-HA Nps were more cytotoxic than free 4-MU on A549 cells. The observed therapeutic activity of 4-MU@FA-PEG-HA Nps on urethane-induced lung cancer model, potentiality revealed a tumor growth inhibition via apoptotic mechanisms and angiogenesis inhibition. The results were supported by Enzyme-linked immunosorbent assay (ELIZA) of transforming growth factors (TGFß1) and serum HA, histopathological analysis as well as immunohistochemical Ki67, CD44, Bcl-2 and caspace-3 staining. Moreover, 4-MU@FA-PEG-HA Nps exhibited a promising safety profile. Hence, it is expected that our developed novel nano-system can be used for potential application on tumor therapy for lung cancer.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Nanocápsulas , Nanopartículas , Antineoplásicos/farmacología , Línea Celular Tumoral , Ácido Fólico , Humanos , Ácido Hialurónico , Himecromona/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Nanocápsulas/uso terapéutico , Polietilenglicoles/uso terapéutico
13.
Polymers (Basel) ; 14(14)2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35890622

RESUMEN

Bisphenol A (BPA) is an xenoestrogenic chemical used extensively in the fabrication of baby bottles, reusable plastic water bottles and polycarbonate plastic containers. The current study aims to investigate the hepatoprotective activity of Moringa oleifera Lam leaf extract (MOLE) and hydrogel NPs made of starch-MOLE-Bovine Serum Albumin (BSA) against Bisphenol A-induced liver toxicity in male rats. Fabrication and characterization of hydrogel NPs formed of starch-MOLE-BSA were investigated using FTIR, TEM, zeta potential, UV-visible spectroscopy and fluorescence spectrophotometer. The potential efficacy of hydrogel NPs was studied. Compared to the results of control, the level of liver function, oxidative stress markers and lipid profile status were remodulated in the groups treated with MOLE and hydrogel NPs (Encap. MOLE). Meanwhile, the administration of MOLE and Encap MOLE significantly increased antioxidant activity and decreased the level of apoptotic pathways. Heme oxygenase (HO)-1 and growth arrest -DNA damage-inducible gene 45b (Gadd45b) were also regulated in the groups treated with MOLE and Encap. MOLE compared to the group which received BPA alone. In the present study, MOLE and hydrogel NPs led to remarkable alterations in histological changes during BPA administration. Overall, MOLE has a potential antioxidant activity which can be used in the treatment of liver disorders.

14.
J Pers Med ; 12(11)2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36579532

RESUMEN

Hepatic fibrosis (HF) is a major cause of liver-related disorders and together with cancer-associated fibroblasts can favor liver cancer development by modulating the tumor microenvironment. Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- ß1, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-ß1 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers. Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- ß1 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy.

15.
Int J Biol Macromol ; 182: 1981-1993, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34058209

RESUMEN

Curcumin is a potential candidate in cancer therapy due to its ability to inhibit many signalling pathways at the same time of exposure because of its unique content of aromatic ring, B diketone, olefinic linker, and O methoxy phenolic groups. Its applications in biomedical therapy is limited because of its sensitivity, and its rapid degradation. In the current study, curcumin inserted into polyelectrolyte pairs (protamine and dextran) and then was functionalized by folic acid conjugated chitosan used for the first time, as theranostic system. Such this strategy allows to improve its mucoadhesion and penetration that increases their accumulation inside cancer cells. CUR-LbL NPs were then used to investigate drug release inside Human Mammary Carcinoma (MCF-7 cell lines) after their incubations for 3 h, 6 h and 24 h. Flow cytometry indicated that the percentages of apoptosis, necrosis and cell cycle arrest were increased significantly in MCF-7 cell lines treated by CUR-LbL NPs. Furthermore, SEM image showed many debris in the section of MCF-7 treated by CUR-LbL NPs. Here, it can be summarized that curcumin functionalized by multi-layered polyelectrolyte capsules can be used as a model to study the fate of the adsorbed nanocarriers and to investigate the drug release inside cells.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quitosano/química , Curcumina/uso terapéutico , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Ácido Fólico/química , Nanopartículas/química , Nanomedicina Teranóstica , Adhesividad , Adsorción , Apoptosis , Neoplasias de la Mama/patología , Neoplasias de la Mama/ultraestructura , Puntos de Control del Ciclo Celular/efectos de los fármacos , Muerte Celular , Forma de la Célula , Curcumina/química , Curcumina/farmacología , Liberación de Fármacos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Nanopartículas/ultraestructura , Necrosis , Invasividad Neoplásica , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Estereoisomerismo
16.
Int J Biol Macromol ; 183: 171-181, 2021 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-33901560

RESUMEN

Many reports have been published recently confirmed the limitation of cargo molecules delivered into the heart. This failure is mostly associated with lymphatic or vascular channels washing or to the immune system recognition. Delivery of anthocyanins by encapsulation may augment it retention in the heart at early time points as the capsules are too large to wash out by lymphatic or venous channels and the physical structure of the capsule may shield the anthocyanins from immunoglobulins and cellular components of the immune system. In the current study, the cardiac dysfunction was induced by using carbon tetrachloride and then animal were treated orally by using anthocyanins incorporated into hydrogel NPs twice time /week for 4 weeks. The results showed anthocyanin loaded hydrogel NPs has ability to re-maintain the glycogen content in the liver and heart tissues of fibrotic group (13 ± 1.4 and 5 ± 0.7 µmol glucose/g tissue). Additionally, MDA and hydroxyproline were significantly reduced. PAS stain showed depletion of glycogen granules from heart tissue. It is concluded that starch based hydrogel loaded by anthocyanins can improve histological cardiac functions after their injury .


Asunto(s)
Antocianinas/farmacología , Cardiomiopatías/tratamiento farmacológico , Glucógeno/metabolismo , Hígado/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Almidón/química , Animales , Antocianinas/química , Tetracloruro de Carbono , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiotoxicidad , Modelos Animales de Enfermedad , Composición de Medicamentos , Fibrosis , Hidrogeles , Hígado/metabolismo , Hígado/patología , Ratones , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Nanopartículas
17.
Int J Biol Macromol ; 182: 1150-1160, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33865895

RESUMEN

In the current study, the treatment efficacy of ECHCAH was evaluated in vitro studies using cell viability and flow cytometry in human TNBCs. The results here showed significant gradual reduction in growth of TNBCs (MDA-231cell lines) after their exposure to serial concentrations for hydrogel assembly (5 µg/mL to 25 µg/mL) for 24 and 48 h, representing (86 ± 1% to 45 ± 1.5% p < 0.001) and (79 ± 1.5% to 35 ± 2.5% p < 0.001) respectively. The flow cytometry showed significant increase in the present of late apoptotic and necrotic cells (64% ± 1.2 and 27% ± 0.3 p < 0.001) after 48 h incubation compared to untreated cells (1.13% ± 0.3 and 4% ± 0.2 p < 0.001) respectively. It can be summarized that ECHCA inside targeted hydrogel assemblies can inhibit proliferation of cancer cells.


Asunto(s)
Carotenoides/química , Quitosano/química , Clorofila/química , Apoptosis/fisiología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Femenino , Citometría de Flujo , Humanos , Hidrogeles/química , Necrosis/metabolismo
18.
Int J Biol Macromol ; 185: 134-152, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34147524

RESUMEN

This study was designed to present a new quercetin encapsulated chitosan functionalized copper oxide nanoparticle (CuO-ChNPs-Q) and assessed its anti-breast cancer activity both in vitro and in vivo. The CuO-ChNPs-Q may act as anti-proliferating agent against DMBA-induced mammary carcinoma in female rats. The CuONPs was functionalized with chitosan then quercetin was conjugated with them producing CuO-ChNPs-Q, then characterized. The in vitro anti-proliferating activity of the CuO-ChNPs-Q was evaluated against three human cell line. Then, the anti-breast cancer effect of the CuO-ChNPs-Q was assessed against DMBA-induction compared to both CuONPs and Q in female rat model. The in vitro results proved the potent anticancer activity of the CuO-ChNPs-Q compared to CuONPs and quercetin. The in vivo data showed significant reduction in breast tumors of DMBA-induced rats treated with CuO-ChNPs-Q compared to CuONPs and Q. The CuO-ChNPs-Q treatment had induced apoptosis via increased p53 gene, arrested the cell-cycle, and increased both cytochrome c and caspase-3 levels leading to mammary carcinoma cell death. Also, the CuO-ChNPs-Q treatment had suppressed the PCNA gene which decreased the proliferation of the mammary carcinoma cells. In conclusion, the CuO-ChNPs-Q might be a promising chemotherapeutic agent for treatment of breast cancer with a minimal toxicity on vital organs.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Quitosano/química , Cobre/química , Quercetina/administración & dosificación , Proteína p53 Supresora de Tumor/metabolismo , 9,10-Dimetil-1,2-benzantraceno/efectos adversos , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/metabolismo , Células CACO-2 , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Células MCF-7 , Nanopartículas del Metal , Antígeno Nuclear de Célula en Proliferación/metabolismo , Quercetina/química , Quercetina/farmacología , Ratas , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Mater Sci Eng C Mater Biol Appl ; 116: 111119, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32806233

RESUMEN

Curcumin is a more efficient polyphenol than many chemotherapeutics. It can inhibit many signaling pathways at the same time resulting in modulation and down regulation for many oncogenic activities, tumor suppressor genes, several transcription factors and their signaling pathways. However it is still not employed as a potential therapeutic tool for cancer treatment. This is due to its hydrophobicity, its hypersensitivity and its poor adsorption. Many trials have been applied for encapsulating curcumin as a delivery system thinking to save its biological benefits. In our recent work, encapsulated curcumin was successfully used to produce bio cross-linkers for mucoadhesive polymer forming multi branched or flower like shape. Moreover, this strategy is not used only to save its biological function, but also to provide a novel bio cross-linker for hydrogel system. This study was investigated by using scanning electron microscopy, FTIR, U-V Visible Spectroscopy. Encapsulated curcumin provides promising bio safe cross-linker for optimizing hydrogel system, since carboxymethyl cellulose raises its ability to penetrate mucus layer. Additionally, flow cytometry and cytotoxicity show ability of encapsulated curcumin to inhibit proliferation of liver cancer cells.


Asunto(s)
Curcumina , Neoplasias Hepáticas , Nanopartículas , Carboximetilcelulosa de Sodio , Curcumina/farmacología , Portadores de Fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico
20.
Pharmaceutics ; 12(5)2020 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-32370293

RESUMEN

: Transforming growth factor-beta (TGFß1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasive and prone to move into the metastatic process. This finding has received great attention for discovering new therapeutic molecules against the TGFß1 pathway. Among many TGFß1 inhibitors, peptides (P17 and P144) were designed to block the TGFß1 pathway. However, their therapeutic applications have limited use, due to lack of selection for their targets and their possible recognition by the immune system and further due to their potential cytotoxicity on healthy cells. Besides that, P144 is a highly hydrophobic molecule with less dissolution even in organic solution. Here, we aimed to overcome the dissolution of P144, as well as design nano-delivery strategies to protect normal cells, to increase cellular penetration and to raise the targeted therapy of both P17 and P144. Peptides were encapsulated in moieties of polymer hybrid protein. Their assembly was investigated by TEM, microplate spectrum analysis and fluorescence microscopy. SMAD phosphorylation was analyzed by Western blot as a hallmark of their biological efficiency. The results showed that the encapsulation of P17 and P144 might improve their potential therapeutic applications.

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