Ciprofloxacin- and levofloxacin-loaded nanoparticles efficiently suppressed fluoroquinolone resistance and biofilm formation in Acinetobacter baumannii.

The spread of fluoroquinolone (FQ) resistance in Acinetobacter baumannii represents a critical health threat. This study aims to overcome FQ resistance in A. baumannii via the formulation of polymeric nanoFQs. Herein, 80 A. baumannii isolates were obtained from diverse clinical sources. All A. baumannii isolates showed high resistance to most of the investigated antimicrobials, including ciprofloxacin (CIP) and levofloxacin (LEV) (97.5%). FQ resistance-determining regions of the gyrA and parC genes were the most predominant resistant mechanism, harbored by 69 (86.3%) and 75 (93.8%) of the isolates, respectively. Additionally, plasmid-mediated quinolone resistance genes aac(6')-Ib and qnrS were detected in 61 (76.3%) and 2 (2.5%) of the 80 isolates, respectively. The CIP- and LEV-loaded poly ε-caprolactone (PCL) nanoparticles, FCIP and FLEV, respectively, showed a 1.5-6- and 6-12-fold decrease in the MIC, respectively, against the tested isolates. Interestingly, the time kill assay demonstrated that MICs of FCIP and FLEV completely killed A. baumannii isolates after 5-6 h of treatment. Furthermore, FCIP and FLEV were found to be efficient in overcoming the FQ resistance mediated by the efflux pumps in A. baumannii isolates as revealed by decreasing the MIC four-fold lower than that of free CIP and LEV, respectively. Moreover, FCIP and FLEV at 1/2 and 1/4 MIC significantly decreased biofilm formation by 47-93% and 69-91%, respectively. These findings suggest that polymeric nanoparticles can restore the effectiveness of FQs and represent a paradigm shift in the fight against A. baumannii isolates.

Design, synthesis, and antitumor activity of PLGA nanoparticles incorporating a discovered benzimidazole derivative as EZH2 inhibitor.

PURPOSE: Targeting enhancer of zeste homolog 2 (EZH2) can represent a hopeful strategy for oncotherapy. Also, the use of PLGA-based nanoparticles as a novel and rate-controlling carrier system was of our concern. METHODS: Benzimidazole derivatives were synthesized, and their structures were clarified. In vitro antitumor activity was evaluated. Then, a modeling study was performed to investigate the ability of the most active compounds to recognize EZH2 active sites. Compound 30 (Drug) was selected to conduct pre-formulation studies and then it was incorporated into polymeric PLGA nanoparticles (NPs). NPs were then fully characterized to select an optimized formula (NP4) that subjected to further evaluation regarding antitumor activity and protein expression levels of EZH2 and EpCAM. RESULTS: The results showed the antitumor activity of some synthesized derivatives. Docking outcomes demonstrated that Compound 30 was able to identify EZH2 active sites. NP4 exhibited promising findings and proved to keep the antitumor activity of Compound 30. HEPG-2 was the most sensitive for both Drug and NP4. Protein analysis indicated that Drug and NP4 had targeted EZH2 and the downstream signaling pathway leading to the decline of EpCAM expression. CONCLUSIONS: Targeting EZH2 by Compound 30 has potential use in the treatment of cancer especially hepatocellular carcinoma.

Innovative coenzyme Q10-loaded nanoformulation as an adjunct approach for the management of moderate periodontitis: preparation, evaluation, and clinical study.

Periodontal diseases are worldwide chronic inflammatory conditions that are associated with heavy production of reactive oxygen species followed by damage of the tooth-supporting tissues. Although the mechanical approach of scaling and root planing (SRP) for removing of plaque is considered as the key element for controlling periodontitis, the anatomical complexity of the teeth hinders accessibility to deeper points. The aim of this study was to design a micellar nanocarrier of coenzyme Q10 (Q10) to support the management of moderate periodontitis. Q10 was formulated in nanomicelles (NMQ10) and evaluated regarding encapsulation efficiency, loading efficiency, percent yield, hydrodynamic size (Dh), polydispersity index (PDI), and zeta potential (ζ potential). NMQ10 was incorporated to in situ gelling systems and the in vitro release of Q10 was studied. A clinical study including evaluation of periodontal parameters and biochemical assay of total antioxidant capacity (T-AOC) and lipid peroxide was achieved. Results revealed that Q10 was efficiently entrapped in spherical-shaped stable NMQ10 with Dh, PDI, and ζ potential of 154.0 nm, 0.108, and - 31.67 mV, respectively. The clinical study revealed that SRP only exhibited improvement of the periodontal parameters. Also, assay of T-AOC and lipid peroxide revealed that their values diminished by 21.5 and 23.8%, respectively. On the other hand, SRP combined with local application of NMQ10 resulted in a significant management of the periodontal parameters, and likewise, the assayed biomarkers proved enhanced antioxidant activity over SRP alone. In conclusion, NMQ10 can be suggested as a promising nanosystem as an approach to support the management of chronic periodontitis. Such results could be used to conduct larger clinical studies. Graphical abstrac.

Validated ion pair chromatographic method for simultaneous determination and in vitro dissolution studies of indacaterol and glycopyrronium from inhaled capsule dosage form.

A rapid, and highly sensitive analytical method were developed for the simultaneous determination of indacaterol maleate (IND) and glycopyrronium bromide (GLY) in their inhaler capsules. Valid ion-pairing chromatographic (IPC) method was performed for separation of GLY in presence of IND using C18 column and mobile phase consisting of acetonitrile: acidified deionized water (60:40% v/v) containing 0.02% sodium dodecyl sulfate (SDS) adjusted to pH 3.0 using OPA (orthophosphoric acid) isocratically eluted at 2.0 mL/min. Quantitation was achieved with UV detection at 210 nm. Cyproheptadine was used as an internal standard. The retention times were 1.9 and 2.5 min for IND, and GLY, respectively. For the IPC method, the calibration graphs were linear in the range of 0.66-66.0 µg/mL for IND and 0.3-30.0 µg/mL for GLY. The proposed method are rapid, reproducible (R.S.D. <2.0%) and achieves satisfactory resolution between IND and GLY (resolution factor = 4.23). The mean recoveries of the analytes in their inhaler capsule were satisfactory. It was applied successfully to in vitro dissolution testing using Franz diffusion cell and extended to a content uniformity test consistent with the United States Pharmacopoeia (USP) guidelines and were found to be precise and accurate for the capsules studied with acceptance value of 4.53 and 1.39 for IND and GLY, respectively.