Background: Ceftriaxone is one of the most common types of antibiotics used to treat most deadly bacterial infections. One way to alleviate the side effects of medication is to reduce drug consumption by changing the ordinary drug forms into nanostructured forms. In this study, a nanostructured lipid carrier (NLC) containing hydrophilic ceftriaxone sodium drug is developed, and its effect on eliminating gram-negative bacteria Escherichia coli death is investigated.Methods: Double emulsion solvent evaporation method is applied to prepare NLC. Mathematical modeling based on the solubility study is performed to select the best materials for NLC preparation. Haftyzer-Van Krevelen and Hoy's models are employed for this purpose. Drug release from optimized NLC is examined under in vitro environment. Then, the efficacy of the optimized sample on eliminating gram-negative bacteria Escherichia coli is investigated. Results: Mathematical modeling reveals that both methods are capable of predicting drug encapsulation efficiency trends by chaining solid and liquid lipids. However, Haftyzer-Van Krevelen's method can precisely predict the particle size trend by changing the surfactant types in water and oily phases of emulsions. The optimal sample has a mean particle size of 86 nm and drug entrapment efficiency of 83%. Also, a controlled drug release in prepared nanostructures over time is observed under in-vitro media. The results regarding the effectiveness of optimized NLC in killing Escherichia coli bacteria suggests that by cutting drug dosage of the nanostructured form in half, an effect comparable to that of free drug can be observed at longer times. Conclusion: Results confirm that NLC structure is an appropriate alternative for the delivery of ceftriaxone drug with a controlled release behavior.

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Nonsyndromic cleft lip with or without palate (CL/P) is thought to be caused by the interplay of genetic and environmental factors, and this has thus hindered the process of identifying genetic causative factors. Numerous studies in the past decade have implicated IRF6 in CL/P, but this has not often been replicated in other populations. In specific, the only etiologic single-nucleotide polymorphism (SNP) identified in the IRF6 locus (rs642961) has recently been shown not to be associated with CL/P in diverse populations. We therefore used a genewide tagging SNP (tagSNP) haplotyping approach (including rs642961 as a tagSNP) to detect all potential risk-conferring haplotypes and combined this with detailed subphenotyping of CL/P cases (N = 150) according to severity. We observed a significant overrepresentation of a tagSNP haplotype carrying the rs642961 risk allele in the most severe subphenotype of CL/P (complete bilateral CL/P; P = 0.008, odds ratio = 4.97, 95% confidence interval = 1.33 to 18.46). It was recently shown that >80% of IRF6 mutations in syndromic CL/P occur on the same haplotype background. We therefore suggest that IRF6 is a marker of CL/P severity.

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