GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells.

The efficient delivery of small interfering RNA (siRNA) to the targeted cells significantly affects the regulation of the overexpressed proteins involved in the progression of several genetic diseases. SiRNA molecules in naked form suffer from low internalization across the cell membrane, high susceptibility to degradation by nuclease enzyme and low stability, which hinder their efficacy. Therefore, there is an urge to develop a delivery system that can protect siRNA from degradation and facilitate their uptake across the cell membrane. In this study, the cationic lipid (GL67) was exploited, in addition to DC-Chol and DOPE lipids, to design an efficient liposomal nanocarrier for siRNA delivery. The physiochemical characterizations demonstrated that the molar ratio of 3:1 has proper particle size measurements from 144 nm to 332 nm and zeta potential of -9 mV to 47 mV that depends on the ratio of the GL67 in the liposomal formulation. Gel retardation assay exhibited that increasing the percentage of GL67 in the formulations has a good impact on the encapsulation efficiency compared to DC-Chol. The optimal formulations of the 3:1 M ratio also showed high metabolic activity against A549 cells following a 24 h cell exposure. Flow cytometry findings showed that the highest GL67 lipid ratio (100 % GL67 and 0 % DC-Chol) had the highest percentage of cellular uptake. The lipoplex nanocarriers based on GL67 lipid could potentially influence treating genetic diseases owing to the high internalization efficiency and safety profile.

Efficient Green Synthesis of (Fe3O4) and (NiFe2O4) Nanoparticles Using Star Anise (Illicium verum) Extract and Their Biomedical Activity against Some Cancer Cells.

Magnetite Fe3O4 and spinel (2:1) and (4:1) NiFe2O4 magnetic nanoparticles (MNPs) were prepared by simple and affordable co-precipitation methods using an extract of star anise (Illicium verum) as a green reducing agent. The morphology and chemical composition of these MNPs were confirmed by field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, UV-visible spectroscopy, and X-ray diffraction (XRD). The synthesized magnetite Fe3O4 and spinel (2:1) and (4:1) NiFe2O4 MNPs were in the size range of 0.1-1 µm. The MNPs had irregular clustered platelets (magnetite Fe3O4) and pyramidal structures (spinel (2:1) and (4:1) NiFe2O4 NPs). The average sizes of the synthesized magnetite Fe3O4, and spinel (2:1) and (4:1) NiFe2O4 MNPs calculated using XRD analysis were 66.8, 72.5, and 72.9 nm, respectively. In addition to the characteristic absorption peaks of magnetite Fe3O4, those of spinel (2:1) and (4:1) NiFe2O4 MNPs were detected at ~300-350 nm and ~700 nm, respectively. Overall, the results of this study indicate that the synthesized magnetite Fe3O4, and spinel (2:1) and (4:1) NiFe2O4 MNPs showed high biomedical activities against liver carcinoma cells and non-small lung adenocarcinoma cells.

Liposome-Encapsulated Tobramycin and IDR-1018 Peptide Mediated Biofilm Disruption and Enhanced Antimicrobial Activity against Pseudomonas aeruginosa.

The inadequate eradication of pulmonary infections and chronic inflammation are significant complications in cystic fibrosis (CF) patients, who usually suffer from persistent and frequent lung infections caused by several pathogens, particularly Pseudomonas aeruginosa (P. aeruginosa). The ability of pathogenic microbes to protect themselves from biofilms leads to the development of an innate immune response and antibiotic resistance. In the present work, a reference bacterial strain of P. aeruginosa (PA01) and a multidrug-resistant isolate (MDR 7067) were used to explore the microbial susceptibility to three antibiotics (ceftazidime, imipenem, and tobramycin) and an anti-biofilm peptide (IDR-1018 peptide) using the minimum inhibition concentration (MIC). The most effective antibiotic was then encapsulated into liposomal nanoparticles and the IDR-1018 peptide with antibacterial activity, and the ability to disrupt the produced biofilm against PA01 and MDR 7067 was assessed. The MIC evaluation of the tobramycin antibacterial activity showed an insignificant effect on the liposomes loaded with tobramycin and liposomes encapsulating tobramycin and IDR-1018 against both P. aeruginosa strains to free tobramycin. Nevertheless, the biofilm formation was significantly reduced (p < 0.05) at concentrations of ≥4 µg/mL and ≤32 µg/mL for PA01 and ≤32 µg/mL for MDR 7067 when loading tobramycin into liposomes, with or without the anti-biofilm peptide compared to the free antibiotic, empty liposomes, and IDR-1018-loaded liposomes. A tobramycin concentration of ≤256 µg/mL was safe when exposed to a lung carcinoma cell line upon its encapsulation into the liposomal formulation. Tobramycin-loaded liposomes could be a potential candidate for treating lung-infected animal models owing to the high therapeutic efficacy and safety profile of this system compared to the free administration of the antibiotic.

Phytosomes as an Emerging Nanotechnology Platform for the Topical Delivery of Bioactive Phytochemicals.

The emergence of phytosome nanotechnology has a potential impact in the field of drug delivery and could revolutionize the current state of topical bioactive phytochemicals delivery. The main challenge facing the translation of the therapeutic activity of phytochemicals to a clinical setting is the extremely low absorption rate and poor penetration across biological barriers (i.e., the skin). Phytosomes as lipid-based nanocarriers play a crucial function in the enhancement of pharmacokinetic and pharmacodynamic properties of herbal-originated polyphenolic compounds, and make this nanotechnology a promising tool for the development of new topical formulations. The implementation of this nanosized delivery system could enhance the penetration of phytochemicals across biological barriers due to their unique physiochemical characteristics, improving their bioavailability. In this review, we provide an outlook on the current knowledge of the biological barriers of phytoconstituents topical applications. The great potential of the emerging nanotechnology in the delivery of bioactive phytochemicals is reviewed, with particular focus on phytosomes as an innovative lipid-based nanocarrier. Additionally, we compared phytosomes with liposomes as the gold standard of lipid-based nanocarriers for the topical delivery of phytochemicals. Finally, the advantages of phytosomes in topical applications are discussed.

Vitamin C and Turmeric Attenuate Bax and Bcl-2 Proteins' Expressions and DNA Damage in Lead Acetate-Induced Liver Injury.

BACKGROUND: Lead is a common environmental and occupational pollutant which induced multiorgans dysfunction. The present study was designed to investigate the hepatoprotective effects of turmeric (TUR) and/or vitamin C (Vit-C) alone or together against lead acetate toxicity and to explore novel molecular pathways. METHOD: Acute hepatotoxicity was induced by lead acetate (100 mg/kg/day, i.p.) in male rats, and the effect of TUR (200 mg/kg/day, orally) and/or Vit-C (250 mg/kg/day, orally) along with lead acetate for 7 days was studied. RESULTS: Lead acetate increased serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, hepatic lipid peroxidation and nitric oxide; while, hepatic superoxide dismutase and glutathione activities were downregulated. Hepatic Bcl-2-associated X (Bax) and B-cell lymphoma-2 (Bcl-2) proteins expressions were altered and hepatic DNA damaged was increased as well. Liver/body weight ratio was decreased. Hematoxylin and eosin demonstrated that lead acetate induced focal areas of massive hepatic degeneration of the hepatocytes. Treatment with both antioxidants ameliorated all the altered parameters and induced marked improvement of liver architecture. CONCLUSION: The combination of TUR and Vit-C has shown the most protective effects against lead acetate-induced hepatotoxicity.