Pharmacokinetics of Afatinib after Intravenous and Oral Administrations in Rats Using Validated UPLC MS/MS Assay.

Afatinib is designated as the first-line management therapy for patients with advanced non-small cell lung cancer, and metastatic head and neck cancer. LC coupled to MS/MS can be utilised in therapeutic drug monitoring to ensure optimal use of Afatinib with the reduction of its possible adverse reactions. The aim of this investigation was to determine the pharmacokinetics of Afatinib in rats after single IV (2 mg/kg) and oral (8 mg/kg) doses. Therefore, a selective, sensitive and precise UPLC MS/MS assay thru electrospray ionisation basis with positive ionisation approach was established to measure Afatinib concentrations in the rat. The precision and accuracy of the developed assay method in the concentration range of 10-1000 ng/ml show no significant difference among inter- and-intra-day analysis (P > 0.05). Linearity was detected over the studied range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of Afatinib in the rat after a single IV dose showed a mean terminal half-life of 4.6 ± 0.97 h, and a mean clearance 480 ± 80 ml/h/kg. After PO administration, a short absorption phase with a mean Tmax of 1.3 ± 0.6 h with the highest concentration of 513.9 ± 281.1 ng/ml, and the lowest concentration detected after 24 h was 18.8 ± 10.7 ng/ml.

New investigation of anti-inflammatory activity of Polycladia crinita and biosynthesized selenium nanoparticles: isolation and characterization.

BACKGROUND: Marine macroalgae have gained interest recently, mostly due to their bioactive components. Polycladia crinita is an example of marine macroalgae from the Phaeophyceae class, also known as brown algae. They are characterized by a variety of bioactive compounds with valuable medical applications. The prevalence of such naturally active marine resources has made macroalgae-mediated manufacturing of nanoparticles an appealing strategy. In the present study, we aimed to evaluate the antioxidant and anti-inflammatory features of an aqueous extract of Polycladia crinita and biosynthesized P. crinita selenium nanoparticles (PCSeNPs) via a carrageenan-induced rat paw edema model. The synthesized PCSeNPs were fully characterized by UV-visible spectroscopy, FTIR, XRD, and EDX analyses. RESULTS: FTIR analysis of Polycladia crinita extract showed several sharp absorption peaks at 3435.2, 1423.5, and 876.4 cm-1 which represent O-H, C=O and C=C groups. Moreover, the most frequent functional groups identified in P. crinita aqueous extract that are responsible for producing SeNPs are the -NH2-, -C=O-, and -SH- groups. The EDX spectrum analysis revealed that the high percentages of Se and O, 1.09 ± 0.13 and 36.62 ± 0.60%, respectively, confirmed the formation of SeNPs. The percentages of inhibition of the edema in pretreated groups with doses of 25 and 50 mg/kg, i.p., of PCSeNPs were 62.78% and 77.24%, respectively. Furthermore, the pretreated groups with 25, 50 mg/kg of P. crinita extract displayed a substantial decrease in the MDA levels (P < 0.00, 26.9%, and 51.68% decrease, respectively), indicating potent antioxidant effect. Additionally, the pretreated groups with PCSeNPs significantly suppressed the MDA levels (P < 0.00, 54.77%, and 65.08% decreases, respectively). The results of immune-histochemical staining revealed moderate COX-2 and Il-1ß expressions with scores 2 and 1 in rats pre-treated with 25 and 50 mg/kg of free extract, respectively. Additionally, the rats pre-treated with different doses of PCSeNPs demonstrated weak COX-2 and Il-1ß expressions with score 1 (25 mg/kg) and negative expression with score 0 (50 mg/kg). Both antioxidant and anti-inflammatory effects were dose-dependent. CONCLUSIONS: These distinguishing features imply that this unique alga is a promising anti-inflammatory agent. Further studies are required to investigate its main active ingredients and possible side effects.

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment.

PURPOSE: Ciprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB). METHODS: NLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined. RESULTS: The CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios (P ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9-5.1 µm. CONCLUSION: Novel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.