Targeted delivery of rifaximin using P6.2-decorated bifunctional PLGA nanoparticles for combating Staphylococcus aureus infections.

The emergence of antibiotic resistance makes the treatment of bacterial infections difficult and necessitates the development of alternative strategies. Targeted drug delivery systems are attracting great interest in overcoming the limitations of traditional antibiotics. Here, we aimed for targeted delivery of rifaximin (RFX) by decorating RFX-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with synthetic P6.2 peptide, which was used as a targeting agent for the first time. Our results showed that encapsulation of RFX into NPs increased its antibacterial activity by improving its solubility and providing controlled release, while P6.2 modification allowed targeting of NPs to S. aureus bacterial cells. A promising therapeutic approach for bacterial infections, these P6.2-conjugated RFX-loaded PLGA NPs (TR-NP) demonstrated potent antibacterial activity against both strains of S. aureus. The antibacterial activity of RFX-loaded PLGA NPs (R-NP) showed significant results with an increase of 8 and 16-fold compared to free RFX against S. aureus and MRSA, respectively. Moreover, the activity of targeted nanoparticles was found to be increased 32 or 16-fold with an MBC value of 0.0078 µg/mL. All nanoparticles were found to be biocompatible at doses where they showed antimicrobial activity. Finally, it revealed that P6.2-conjugated targeted nanoparticles extremely accumulated in S. aureus rather than E. coli.

Blend Electrospinning of Nigella sativa-Incorporating PCL/PLA/HA Fibers and Its Investigation for Bone Healing Applications.

One of the well-known postoperative complications that requires a number of prophylactic and curative treatments is infection. The implications of postsurgical infections are further exacerbated by the emergence of antibiotic-resistant strains. Reduced effectiveness of synthetic antibiotics has led to an interest in plant-based substances. Extracts obtained from Nigella sativa have been shown to possess effective anti-infectious agents against bacteria frequently seen in bone infections. In this study, a fiber-based bone scaffold containing polycaprolactone, poly(lactic acid), and hydroxyapatite with N. sativa oil at varying concentrations was developed. Solvent electrospinning was used to fabricate the fibers with the specified composition. According to FE-SEM analysis, fibers with average diameters of 751 ± 82, 1000 ± 100, 1020 ± 90, and 1223 ± 112 nm were formed and successful integration of N. sativa oil into the fiber's structure was confirmed via FTIR. Staphylococcus aureus showed moderate susceptibility against the fibers with a maximum inhibition zone diameter of 11.5 ± 1.6 mm. MTT assay analysis exhibited concentration-dependent cell toxicity against fibroblast cells. In short, the antibacterial fibers synthesized in this study possessed antibacterial properties while also allowing moderate accommodation of CDD fibroblast cells at low oil concentrations, which can be a potential application for bone healing and mitigating postsurgical infections.

Host-Guest Interactions of Caffeic Acid Phenethyl Ester with ß-Cyclodextrins: Preparation, Characterization, and In Vitro Antioxidant and Antibacterial Activity.

The aim of this study is to improve the solubility, chemical stability, and in vitro biological activity of caffeic acid phenethyl ester (CAPE) by forming inclusion complexes with ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (Hß-CD) using the solvent evaporation method. The CAPE contents of the produced complexes were determined, and the complexes with the highest CAPE contents were selected for further characterization. Detailed characterization of inclusion complexes was performed by using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and electrospray ionization-mass spectrometry (ESI-MS). pH and thermal stability studies showed that both selected inclusion complexes exhibited better stability compared to free CAPE. Moreover, their antimicrobial activities were evaluated against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) for the first time. According to the broth dilution assay, complexes with the highest CAPE content (10C/ß-CD and 10C/Hß-CD) exhibited considerable growth inhibition effects against both bacteria, 31.25 µg/mL and 62.5 µg/mL, respectively; contrarily, this value for free CAPE was 500 µg/mL. Furthermore, it was determined that the in vitro antioxidant activity of the complexes increased by about two times compared to free CAPE.

A nanotechnological approach in the current therapy of COVID-19: model drug oseltamivir-phosphate loaded PLGA nanoparticles targeted with spike protein binder peptide of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is today's most serious epidemic disease threatening the human race. The initial therapeutic approach of SARS-CoV-2 disease is based upon the binding the receptor-binding site of the spike protein to the host cell's ACE-2 receptor on the plasma membrane. In this study, it is aimed to develop a biocompatible and biodegradable polymeric drug delivery system that is targeted to the relevant receptor binding site and provides controlled drug release. Oseltamivir phosphate (OP) is an orally administered antiviral prodrug for primary therapy of the disease in biochemically activated carboxylate form (oseltamivir carboxylate OC). In the presented study, model drug OP loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) targeted with spike-binding peptide 1 (SBP1) of SARS-CoV-2 were designed to be used as an efficient and prolonged released antiviral drug delivery system. RY, EE, and DL values of the OP-loaded NPs produced by the solvent evaporation method were calculated to be 59.3%, 61.4%, and 26.9%, respectively. The particle size of OP-loaded NPs and OP-loaded NPs targeted with SBP1 peptide were 162.0 ± 11.0 and 226.9 ± 21.4 nm, respectively. While the zeta potential of the produced OP-loaded NPs was achieved negatively -23.9 ± 1.21 mV), the result of the modification with SBP1 peptide this value approached zero as -4.59 ± 0.728 mV. Morphological features of the OP-loaded NPs were evaluated using FEG-SEM. The further characterization and surface modification of the NPs were analyzed by FT-IR.In-vitrorelease studies of NPs showed that sustained release of OP occurred for two months that fitting the Higuchi kinetic model. By evaluating these outputs, it was reported that surface modification of OP-loaded NPs was significantly effective on characteristics such as size, zeta potential values, surface functionality, and release behavior. The therapeutic model drug-loaded polymeric formulation targeted with a specific peptide may serve as an alternative to more effective and controlled release pharmaceuticals in the treatment of COVID-19 upon an extensive investigation.