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1.
Poult Sci ; 101(12): 102162, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36191516

ABSTRACT

The purpose of this study was to investigate the production performance, antioxidant parameters, egg yolk cholesterol content, and expression of genes related to cholesterol metabolism in laying hens fed L-carnitine (LC) and L-carnitine-loaded solid lipid nanoparticles (LC-SLNs). A total of 350 Hy-Line (w-36) laying hens at 50 wk of age (1520.0 ± 0.7 g) were randomly assigned to 35 units (5 replicates and 50 hens in each treatment) with seven dietary treatments as a completely randomized design. The dietary treatments were corn-soybean meal-based diets, including 1) Control (basal diet); 2) Basal diet +50 mg/kg LC (50LC); 3) Basal diet +100 mg/kg LC (100LC); 4) Basal diet +150 mg/kg LC (150LC); 5) Basal diet +50 mg/kg LC-SLNs (50LC-SLNs); 6) Basal diet +100 mg/kg LC-SLNs (100LC-SLNs) and 7) Basal diet +150 mg/kg LC-SLNs (150LC-SLNs). Results showed that the 50LC-SLNs had the least feed conversion ratio (FCR) in all groups (P < 0.05). The dietary supplementation of 100LC-SLNs decreased (P < 0.01) the egg yolk cholesterol concentration from 14.71 to 11.76 mg/g yolk (25%). The 50LC-SLNs group produced the most total antioxidant capacity with a difference of 58.44% compared to the control group (P < 0.01). The greatest amount of total superoxide dismutase was found for 50LC-SLNs (P < 0.05), while the glutathione peroxidase was not affected by the experimental treatments (P > 0.05). Serum malondialdehyde levels were reduced by 50.52% in laying hens fed 50LC-SLNs compared to the control group (P < 0.05). The transcript level of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly decreased (P < 0.01) in the LC and LC-SLNs groups. The expression of cholesterol 7α-hydroxylase was significantly increased (P < 0.01) in the plain LC (∼83%) and LC-SLNs (∼91%) groups. The inclusion of LC-SLNs in the diet increased (P < 0.05) the villus height and decreased villus width in all three parts of the small intestine. Dietary inclusion of LC was found to reduce egg yolk and serum cholesterol content by improving the production performance and antioxidant status. The LC-SLNs groups were more affected than the plain LC groups, which may be attributed to the increased bioavailability of LC.


Subject(s)
Animal Feed , Antioxidants , Animals , Female , Antioxidants/metabolism , Animal Feed/analysis , Chickens/genetics , Chickens/metabolism , Dietary Supplements , Carnitine/pharmacology , Diet/veterinary , Cholesterol
2.
Colloids Surf B Biointerfaces ; 212: 112365, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35124408

ABSTRACT

L-carnitine (LC) is a highly water-soluble compound involved in the ß-oxidation of lipids and transportation of long-chain fatty acids across the membrane of mitochondria. However, the higher hydrophilicity of LC limits its free diffusion across the bilayer lipid membrane of intestinal epithelium in oral administration, decreasing oral bioavailability. Drug delivery with nanoparticles enhances cargo bioavailability and cellular uptake and improves therapeutic outcomes while decreasing unwanted side effects. Here, we proposed solid lipid nanoparticles (SLNs) as a hydrophobic carrier for LC delivery, aiming at increasing LC bioavailability and its protective role against intracellular oxidative stress damages. The LC-SLNs were prepared using the hot homogenization technique, and different physicochemical properties were investigated. The inhibition of H2O2-induced ROS generation in human umbilical vein endothelial cells (HUVECs) with plain LC and LC-SLNs was investigated. Moreover, various in vitro experiments were performed to assess whether LC-SLNs can protect HUVECs from H2O2-induced genotoxicity and apoptosis. The monodispersed and spherical blank SLNs and LC-SLNs were 104 ± 1.8 and 128 ± 1.5 nm, respectively with a drug loading (DL) of 11.49 ± 0.78 mg/mL and acceptable encapsulation efficiency (EE%) (69.09 ± 1.12) of LC-SLNs. The formulation process did not affect the antioxidant properties of LC. MTT assay and comet assay demonstrated that the LC-SLNs decreased cytotoxicity and genotoxicity of H2O2, respectively on HUVECs. Besides, LC-SLNs more inhibited ROS generation, along with apoptotic events in H2O2-treated HUVECs compared to the plain LC. Altogether, our findings affirmed the protective effects of LC-SLNs against H2O2-induced genotoxicity and apoptosis in HUVECs. In conclusion, LC-SLN formulation is a promising drug delivery system to overcome the bioavailability issue of hydrophilic LC, enhancing the antioxidant and biological properties of the plain LC.


Subject(s)
Hydrogen Peroxide , Nanoparticles , Apoptosis , Carnitine/pharmacology , Drug Carriers/chemistry , Human Umbilical Vein Endothelial Cells , Humans , Hydrogen Peroxide/pharmacology , Lipids/chemistry , Liposomes , Nanoparticles/chemistry , Particle Size
3.
Pharm Dev Technol ; 26(9): 934-942, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34338582

ABSTRACT

Acriflavine (ACF) is an antiseptic compound with the potential antitumor activity which is used for the fluorescent staining of RNA due to its dominant fluorescent emission at ∼515 nm. Here, solid lipid nanoparticles (SLNs) containing ACF (ACF-SLNs) were prepared and their physicochemical properties, potential geno/cytotoxicity, as well as the fluorescent properties were investigated. FITC-annexin V/PI staining and cell cycle assays were carried out to find the type of cellular death caused. Particle size analysis and SEM images revealed that spherical ACF-SLNs had a homogeneous dispersion with a mean diameter of 106 ± 5.7 nm. Drug loading (DL) of 31.25 ± 4.21 mg/mL and high encapsulation efficiency (EE%) (89.75 ± 5.44) were found. ACF-SLNs physically were relatively stable in terms of dispersion, size, and EE. The uptake study demonstrated the potential use of fluorescent ACF-SLNs in bio-distribution studies. MTT assay showed that plain ACF could induce growth inhibition of A549 cells with IC50 of 8.5, 6, and 4.5 µMol after 24, 48, and 72 hours, respectively, while ACF-SLNs had stable cytotoxic effects after 48 hours. ACF-SLNs induced remarkable apoptosis and even necrosis after 48 h. Conclusively, ACF-SLNs with acceptable physicochemical features showed increased bioimpacts after 48 h compared to plain ACF.


Subject(s)
Acriflavine/chemical synthesis , Anti-Infective Agents, Local/chemical synthesis , Cell Proliferation/drug effects , Chemistry, Pharmaceutical/methods , Liposomes/chemical synthesis , A549 Cells , Acriflavine/pharmacology , Anti-Infective Agents, Local/pharmacology , Cell Proliferation/physiology , Cell Survival/drug effects , Cell Survival/physiology , Humans , Liposomes/pharmacology , Nanoparticles , Particle Size
4.
Chem Phys Lipids ; 239: 105123, 2021 09.
Article in English | MEDLINE | ID: mdl-34403685

ABSTRACT

Lawsone (LWS) is a naphthoquinone-type dye with potential antitumor activity. LWS is used in cosmetics for coloring hair, skin, and nails. In this study, solid lipid nanoparticles (SLNs) containing LWS were prepared using a hot homogenization technique. Physicochemical properties of LWS-SLNs including encapsulation efficiency (EE), drug loading (DL), size, zeta potential, homogeneity, in vitro release, and kinetics of release were determined. The potential cytotoxic properties of LWS-SLNs were investigated. Comet assay was done to assess the genotoxicity of LWS-SLNs. The scanning electron microscopy (SEM) images revealed that LWS-SLNs were spherical and homogeneously dispersed. The average diameter of free SLNs and LWS-SLNs were 97 ± 1.4 and 127 ± 3.1 nm, respectively with high EE% (95.88 ± 3.29) and a DL of 22.72 ± 1.39 mg/mL of LWS-SLNs. The plain LWS could induce growth inhibition of A549 cells with IC50 of 17.99 ± 1.11, 13.37 ± 1.22, and 9.21 ± 1.15 µg/mL after 24, 48, and 72 h, respectively, while LWS-SLNs had more cytotoxic effects after 48 h (9.81 ± 1.3 µg/mL). Comet assay represented clear fragmentation in the chromatin of the treated cells. Besides, LWS-SLNs (13.37 ± 1.22 µg/mL) induced ∼52 % apoptosis and even necrosis after 48 h. The qPCR results showed an enhanced downregulation of Bcl-2 and upregulation of Casp 9 due to the treatment of A549 cells with LSW-SLNs. In conclusion, a stable formulation of LWS-SLN was prepared with good physicochemical features and long-term biological effects that candidate it for in vivo trials.


Subject(s)
Antineoplastic Agents/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , Naphthoquinones/chemistry , A549 Cells , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Death/drug effects , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Liberation , Gene Expression Regulation, Neoplastic/drug effects , Humans , Kinetics , Naphthoquinones/metabolism , Naphthoquinones/pharmacology , Particle Size
5.
Adv Pharm Bull ; 9(3): 393-400, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31592432

ABSTRACT

Purpose: This study aimed to improve the pharmacokinetic behavior of polyunsaturated fatty acids (PUFAs) oxidation to enhance oxidative stability for inhibiting formation of toxic hydroperoxides, develops off-flavors and shortens shelf-life. Methods: Nanostructured lipid carrier (NLC) co-encapsulating omega-3 fish oil and α-tocopherol was successfully prepared by melt blending and hot sonication method to enhance the oxidative stability of the fish oil. Encapsulation efficiency (EE) and in vitro release, the oxidative stability of prepared nanoparticles (NPs) were measured using detection of peroxide value (PV) and thiobarbituric acid (TBA) during 40 days. Results: Electron microscopy and particle size analysis showed dispersed and homogenous NPs with an average diameter of 119 nm. Sustained oil release at a physiologic pH, and longterm stability in terms of the size, zeta, and dispersity of NPs was achieved after 75 days of storage. The omega-3 fish oil co-encapsulated with α-tocopherol in the NLC possessed better oxidative stability compared with the all other formulations. Also, it was found that the NLC as an encapsulation method was more successful to inhibit the formation of the primary oxidation products than the secondary oxidation products. Conclusion: Generally, these findings indicated that co-encapsulation of fish oil and α-tocopherol within the NLC can be a suitable delivery system in order to enrich foodstuffs, in particular clear beverages.

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