Pharmacokinetics, Tissue Distribution and Excretion of Ag2S Quantum Dots in Mice and Rats: the Effects of Injection Dose, Particle Size and Surface Charge.

PURPOSE: We systematically investigated the effects of injection dose, particle size and surface charge on the pharmacokinetics, tissue distribution and excretion of Ag2S quantum dots (Qds) in rats and mice. METHODS: Three different doses of Ag2S Qds with similar size and composition were administrated to rats and mice. The effect of size and surface charge was investigated with the injection of three sizes (5, 15 and 25 nm) of Ag2S Qds possessing similar surface charge, as well as 5 nm Qds with a positive surface charge. RESULTS: Results indicated that pharmacokinetics and biodistribution of Ag2S Qds were strongly dose, particle size and surface charge dependent. By increasing the dose from 0.5 to 4.0 mg/kg, mean residence time (MRT) and apparent volume of distribution at steady state (Vss) were increased while clearance (CL) was decreased. Qds with a negative surface charge had significantly larger MRT and Vss values than positively charged particles, but their CL was about 50% lower than that of positively charged ones. By increasing Qds size from 5 to 25 nm, CL was increased while MRT and AUC were decreased. CONCLUSIONS: This study establishes comprehensive principles for the rational design and tailoring of Ag2S Qds for biomedical applications. Graphical Abstract The effects of injection dose, particle size and surface charge on pharmacokinetics and tissue distribution of Ag2S Qds after intravenous injection into rats and mice were investigated.

Novel genetic variants data for adaptation to hypoxia in native chickens.

OBJECTIVE: The genomic response and the role of genetic variants in hypoxia condition are always interesting issues about adaption pathways at genomic level. Herein, we carried out a comparative genomic study between highland and lowland native chickens, in order to identify the adaptive variants in hypoxia condition. We generated more than 20 million genetic variants in highland and lowland chickens. Finally, 3877 SNVs including the mtDNA ones, were discovered as novel adaptive genetic variants. The generated data set can provide new insight about mechanism of adaptation to hypoxia at genomic level. DATA DESCRIPTION: To investigate the role of genetic variants in adaptation to hypoxia, 10 whole-genome sequencing data sets associated to highland and lowland native chickens were provided. DNA was extracted by salting-out protocol. Paired-end 125 bp short reads were sequenced by Illumina Hiseq 2000. Variants calling of highland and lowland native chickens were performed by fix ploidy algorithm in CLC Genomic Workbench. Total genetic variants of highland chickens were compared to lowland chickens in order to identify the differential genetic variants (DGVs) between highland and lowland chickens. In this way, 3877 novel SNVs (VCF format) including the mtDNA ones, were deposited at EBI database ( https://identifiers.org/ena.embl:ERZ491574 ) for the first time.

Doxorubicin-Loaded Multivesicular Liposomes (DepoFoam) as a Sustained Release Carrier Intended for Locoregional Delivery in Cancer Treatment: Development, Characterization, and Cytotoxicity Evaluation.

Background: Despite the advantages of direct intratumoral (IT) injection, the relatively rapid withdrawal of most anti-cancer drugs from the tumor due to their small molecular size limits the effectiveness of this method of administration. To address these limitations, recently, increasing attention has been directed to using slow-release biodegradable delivery systems for IT injection. Objectives: This study aimed to develop and characterize a doxorubicin-loaded DepoFoam system as an efficient controlled-release carrier to be employed for locoregional drug delivery in cancer treatment. Methods: Major formulation parameters, including the molar ratio of cholesterol to the main lipid [Chol/egg phosphatidylcholine (EPC)], triolein (TO) content, and lipid-to-drug molar ratio (L/D), were optimized using a two-level factorial design approach. The prepared batches were evaluated for encapsulation efficiency (EE) and percentage of drug release (DR) after 6 and 72 hours as dependent variables. The optimum formulation (named DepoDOX) was further evaluated in terms of particle size, morphology, zeta potential, stability, Fourier-transform infrared spectroscopy, in vitro cytotoxicity, and hemolysis. Results: The analysis of factorial design indicated that TO content and L/D ratio had a negative effect on EE; between these two, TO content had the greatest effect. The TO content was also the most significant component, with a negative effect on the release rate. The ratio of Chol/EPC showed a dual effect on the DR rate. Using a higher percentage of Chol slowed down the initial release phase of the drug; nevertheless, it accelerated the DR rate in the later slow phase. DepoDOX were spherical and honeycomb-like structures (≈ 9.81 µm) with a desired sustained release profile, as DR lasted 11 days. Its biocompatibility was confirmed by the results of cytotoxicity and hemolysis assays. Conclusions: The in vitro characterization of optimized DepoFoam formulation demonstrated its suitability for direct locoregional delivery. DepoDOX, as a biocompatible lipid-based formulation, showed appropriate particle size, high capability for encapsulating doxorubicin, superior physical stability, and a markedly prolonged DR rate. Therefore, this formulation could be considered a promising candidate for locoregional drug delivery in cancer treatment.

Effect of Surfactant Type, Cholesterol Content and Various Downsizing Methods on the Particle Size of Niosomes.

The present study was conducted to investigate the performance of different size reduction techniques including probe sonication, extrusion, and high pressure homogenization for nanosizing of niosomes. Also, the effects of cholesterol content and surfactant type on the size and poly dispersity index (PDI) of the formulations were evaluated. Various niosomal formulations composed of Brij 72, Span 60, or Tween 60 were prepared and then, to reduce vesicle size and minimize the PDI, the niosomes were treated by various post-processing procedures. Surfactant type showed a significant effect on the particle size of the niosomes. The particle size of Tween 60 niosomes was significantly larger than those of Span 60 and Brij 72 niosomes (P < 0.05), indicating that at the same cholesterol content, niosomes composed of a surfactant with a higher HLB value show larger particle size than those with a lower HLB value. The influences of cholesterol content as well as downsizing methods, on the particle size and distribution of niosomes were significantly dependent on the surfactant composition of the niosomes. Extrusion and probe sonication were found to be the most efficient methods for size reduction of the Tween 60 and Span 60 niosomes, while for downsizing of Brij 72 niosomes, all employed methods were efficient and resulted in the approximately similar size of about 200 nm. In conclusion, the selection of an efficient method for nanosizing of niosomes and also achievement of a desired size range, and homogeneity highly depends on the niosome composition, particularly on the employed surfactant type.

Theranostic niosomes for direct intratumoral injection: marked enhancement in tumor retention and anticancer efficacy.

AIM: For simultaneous bioimaging and drug delivery via direct intratumoral injection, doxorubicin and Ag2S quantum dots co-loaded multifunctional niosomes were prepared and fully characterized. MATERIALS & METHODS: Various theranostic niosomes were prepared and investigated regarding cytotoxicity, in vivo imaging, drug accumulation in breast cancer tumor and antitumor activity. RESULTS: Niosomes composed of Tween-60, Tween-80 or Span 60 produced strong and more durable detectable fluorescence signals. Despite a higher accumulation of Tween-60 niosomes in tumor, the Span 60 formulation showed the highest antitumor efficacy when compared with the free drug (71.7 and 20.3% inhibition in tumor growth, respectively). CONCLUSION: Direct intratumoral injection of theranostic niosomes with appropriate composition could be a powerful tool for combined multimodal imaging and therapy.