Assessment of the therapeutic potential of lutein and beta-carotene nanodispersions in a rat model of fibromyalgia.

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and cognitive impairment. Despite the availability of various treatment options, FM remains a challenging condition to manage. In the present study, we investigated the efficacy of formulated nanodispersions of lutein and beta-carotene in treating FM-related symptoms induced by reserpine in female Wistar rats. Several techniques have been implemented to assess this efficacy at various levels, including biochemical, bioelectrical, and behavioral. Namely, oxidative stress markers, monoamine levels, electrocorticography, pain threshold test, and open field test were conducted on control, FM-induced, and FM-treated groups of animals. Our results provided compelling evidence for the efficacy of carotenoid nanodispersions in treating FM-related symptoms. Specifically, we found that the dual action of the nanodispersion, as both antioxidant and antidepressant, accounted for their beneficial effects in treating FM. With further investigation, nano-carotenoids and particularly nano-lutein could potentially become an effective alternative treatment for patients with FM who do not respond to current treatment options.

Stress impact of liposomes loaded with ciprofloxacin on the expression level of MepA and NorB efflux pumps of methicillin-resistant Staphylococcus aureus.

One mechanism of ciprofloxacin resistance is attributed to chromosomal DNA-encoded efflux pumps such as the MepA and NorB proteins. The goal of this research is to find a way to bypass Staphylococcus aureus' efflux pumps. Because of its high membrane permeability and low association with NorB and MepA efflux proteins, a liposome-encapsulating antibiotic is one of the promising, cost-effective drug carriers and coating mechanisms for overcoming active transport of methicillin-resistant S. aureus (MRSA) multidrug-resistant efflux protein . The calculated "Log Perm RRCK" membrane permeability values of 1,2-distearoyl-sn-glycerol-3-phosphocholine (DSPC) ciprofloxacin liposome-encapsulated (CFL) showed a lower negative value of - 4,652 cm/s and greater membrane permeability than ciprofloxacin free (CPF). The results of RT-qPCR showed that cationic liposomes containing ciprofloxacin in liposome-encapsulated form (CFL) improved CPF antibacterial activity and affinity for negatively charged bacterial cell surface membrane in comparison to free drug and liposome, as it overcame several resistance mechanisms and reduced the expression of efflux pumps. Ciprofloxacin liposome-encapsulated (CFL) is therefore more effective than ciprofloxacin alone. Liposomes can be combined with a variety of drugs that interact with bacterial cell efflux pumps to maintain high sustained levels of antibiotics in bacterial cells.

Enhanced cytotoxic activity of beta carotene conjugated liposomes towards breast cancer cell line: comparative studies with cyclophosphamide.

This work aims to evaluate cyclophosphamide (Cyclo) cytotoxic efficacy combined with liposomes in the presence or absence of beta carotene (beta) by detecting the effects of these compounds on the breast cancer cell line (MCF-7) DNA damage. The IC50 value for beta in cytotoxic assay with MCF-7 treated cells was 21.15 µg/ml, while with liposomal beta (LipoBeta) being 121 µg/ml. The free Cyclo IC50 value was 719.86 µg/ml, its liposomal form (LipoCyclo) was 172 µg/ml. The results indicated that in contrast with Cyclo and control values, all comet assay parameters for the LipoBeta were significantly increased (P < 0.05). In MCF-7 cells treated with beta, the findings show a higher intensity of comet tail than those treated with LipoBeta. The presence of several double-strand breaks suggests this high intensity relative to the head. The molecular combination between Cyclo and liposomes in the presence or absence of beta was characterized. Dynamic light scattering measurements confirmed the mono-dispersity of all samples. The incorporation of Cyclo or beta into liposomes exhibited a slight shift to higher temperature compared to the main peak of empty liposomes that exists at 101.5°C which creates a conformational disorder within the phospholipids. The FTIR study showed structural alterations in vesicles after liposome encapsulation.

Cationic liposome-encapsulated carotenoids as a potential treatment for fibromyalgia in an animal model.

The present study investigated the efficacy of cationic liposome-encapsulated carotenoids (lutein or beta-carotene) as a treatment in an animal model of fibromyalgia (FM). Preparation and characterization of the nano-sized cationic liposomal carotenoids have been carried out. FM has been induced in the experimental animals via successive subcutaneous reserpine injection (1 mg/kg). Animals were divided into four groups; control, reserpinized (Res), reserpinized and cationic liposomal lutein-treated (Res + CL-Lut), and reserpinized and liposomal beta-carotene-treated (Res + CL-Bc). Levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT), and oxidative stress markers (MDA, H2O2, NO, and GSH) were determined in the brain's cortical tissue of the different groups of animals. Furthermore, the spectral analysis of the electrocorticogram (ECoG) was carried out. Animal behavior was tested for different animal groups. Results showed a significant reduction in monoamines, an elevation of oxidative stress markers, a shift in the ECoG frequency band power, and a change in pain threshold of the reserpinized animals. A return to a non-significant difference from the control values of all the measured parameters has been obtained after two weeks of cationic liposomal carotenoid preparations treatment. The present findings shed more light on the validity of the reserpine model of FM and provide evidence for the antidepressant, antioxidant, and anti-nociceptive potential of the cationic liposomal carotenoids. The present results proofed that the natural product preparations on a nano-sized scale could be a good alternative to the pharmacological interventions for FM treatment.

Biophysical characterization of lutein or beta carotene-loaded cationic liposomes.

The interactions between carotenoids and membrane constituents are vital for understanding the mechanism of their dynamic action. Lutein and beta-carotene were loaded separately into the bilayer of dipalmitoylphosphatidylcholine (DPPC) mixed at a molar ratio with l-α-phosphatidylethanolamine derived from sheep brain (cephalin) and stearylamine (SA) to form cationic liposomes. The molecular interaction between lutein or beta-carotene with cationic liposomes was studied using transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. Encapsulation efficiency (EE %) and in vitro drug release were determined. The DLS measurements confirmed the mono-dispersity of all samples. TEM results revealed that liposomal samples were oval-shaped and there was a change in their morphology and size upon encapsulation of lutein or beta-carotene. Beta-carotene was observed to adhere to the boundary surface within the liposomal assembly with external morphological alterations. EE% of lutein and beta-carotene exceeded 98.8 ± 0.3% and 87 ± 4%, respectively. Lutein doped with cationic liposomes shows better in vitro release stability (about 30%) than beta-carotene (about 45%) between the 3rd and the 6th hour manifested by lower leakage rate percentage of lutein which would lead to higher lutein retention. The incorporated lutein resulted in broadening and shifting of the major endothermic peak of the co-liposomes, while the incorporation of beta-carotene did not induce a noticeable shift. An FTIR study was employed to reveal structure alterations in the vesicles after the encapsulation of lutein or beta-carotene into liposomes. Encapsulation of lutein or beta-carotene into liposomes induced a change in the frequency of the symmetric and asymmetric CH2 stretching bands in the acyl chain that may influence the order of the membrane.