Both Nigella sativa oil and atorvastatin possess anti-inflammatory, immunomodulatory, antioxidant, and antibacterial properties that benefit wound healing. In this work, chitosan–carboxymethyl cellulose was loaded on N. sativa oil to synthesize oil nanogel (ONG) which was later used to load with atorvastatin to obtain atorvastatin-oil nanogel (ATONG). Evaluation of the particle size of ONG and ATONG proved the average of 172 and 193 nm, and their surface charges were found to be 32.2 and 34.7 mV, respectively. Transmission electron microscopy of the sample showed that the particles had homogeneous size distributions with spherical structures. Moreover, drug loading efficiency, drug release, and stability of ATONG were investigated, and their results confirmed the appropriate loading and release of atorvastatin. Cytotoxicity evaluation demonstrated that ATONG can safely release atorvastatin intracellularly in fibroblasts. Results from in vitro skin permeation of ONG and ATONG also revealed that the nanogels (NGs) has proper flux through the skin layers. The in vitro wound closure assay for ATONG verified the proliferation and migration capabilities of fibroblasts, confirming the positive effect on wound-healing applications. In scratch model of fibroblasts, the treatment with ATONG resulted in an increase in the expression of the FGF2, TGF-β1, and VEGF genes involved in fibroblast proliferation and migration aimed at wound healing (p < .001). ATONG, also demonstrated bactericidal effects against Staphylococcus, S. aureus, and S. epidermidis species. Based on the results, ONG and ATONG exhibited great potential to be used as a transdermal drug carrier and skin wound healing NG, respectively.

Background: Polymorphism ofCYP2C19gene is one of the important factors in pharmacokinetics of CYP2C19 substrates. Omeprazole is a proton pump inhibitor which is mainly metabolized by cytochrome P450 2C19 (CYP2C19). The aim of present study was to assess omeprazole hydroxylation index as a measure of CYP2C19 activity considering new variant allele (CYP2C19*17) in Iranian population and also to see if this activity is sex dependent.Methods: One hundred and eighty healthy unrelated Iranian individuals attended in this study. Blood samples for genotyping and phenotyping were collected 3 hours after administration of 20 mg omeprazole orally. Genotyping of2C19variant alleles*2,*3and*17was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and semi-nested PCR methods. Plasma concentrations of omeprazole and hydroxyomeprazole were determined by high performance liquid chromatography (HPLC) technique and hydxroxylation index (HI) (omeprazole/ hydroxyomeprazole) was calculated.Results: TheCYP2C19*17was the most common variant allele in the studied population (21.6%). Genotype frequencies ofCYP2C19*17*17,*1*17, and*2*17were 5.5%, 28.8% and 3.3% respectively. The lowest and the highest median omeprazole HI was observed in*17*17and*2*2genotypes respectively (0.36 vs. 13.09). The median HI of omeprazole in subjects homozygous forCYP2C19*1was 2.16-fold higher than individuals homozygous forCYP2C19*17(P < 0.001) and the median HI ofCYP2C19*1*17genotype was 1.98-fold higher thanCYP2C19 *17*17subjects (P < 0.001). However, subjects withCYP2C19*2*17(median HI: 1.74) andCYP2C19*1*2(median HI: 1.98) genotypes and alsoCYP2C19*1*17(median HI: 0.71) andCYP2C19*1*1(mean HI: 0.78) did not show any significantly different enzyme activity. In addition, no statistically significant difference was found between women and men in distribution ofCYP2C19genotypes. Furthermore, the hydroxylation index of Omeprazole was not different between women and men in the studied population.Conclusion: Our data point out the importance ofCYP2C19*2andCYP2C19*17variant alleles in metabolism of omeprazole and therefore CYP2C19 activity. Regarding the high frequency ofCYP2C19*17in Iranian population, the importance of this new variant allele in metabolism of CYP2C19 substrates shall be considered.