Nanotechnology and nanoparticles (NPs) have increasingly been studied as an alternative for antibiotics because of the feasibility to be used in implantable devices both for bacterial detection and infection prevention. The low rate of resistance development against NPs because of its multiple mode of action has contributed to its increased acceptance in clinical setting. Further development of NPs and their anticancer activity against many human cancer cell lines including breast and ovarian have been documented. Fe₂O₃-NPs could be used for antibacterial and anticancer activity assessment. Iron oxide, apart from being available extensively and cheap, also plays a role in multiple biological processes, making it an interesting metal for NPs. The aim of the present study revolves around generation and characterization of iron oxide Fe₂O₃-NPs, followed by assessment of its antimicrobial and anticancer activities. Synthesis of Fe₂O₃-NPs was performed by hydrothermal approach, and its characterization was done by UV-visible, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) analyses, and transmission electron microscopy (TEM). Antimicrobial activity was checked by agar diffusion assay against Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans. Anticancer activity of the NPs was assessed using the human cancer cell lines including cervical carcinoma cell line (HeLa) and MCF7. The developed Fe₂O₃-NPs exhibited a characteristic absorption curve in the 500-600nm wavelength range by UV-visible analysis, the XRD peaks were found to index the rhombohedral shape, and the FTIR analysis ascertained the bonds and functional groups at wavenumber from 400 to 4000cm^-1. Antimicrobial assay detected significant effect against Staphylococcus aureus and Bacillus subtilis with zones of inhibition: 21 and 22mm, respectively. Likewise, Fe₂O₃-NPs show good activity towards tested fungal strain Candida albicans with zone of inhibition of 24mm. The 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay identified significant anticancer activity of the NPs against both cell lines. Our study documents the successful generation and characterization of Fe₂O₃-NPs having excellent antimicrobial and anticancer activities.

This study investigates the development of topically applied non-invasive chitosan-nanoparticles (CSNPs) for ocular delivery of tedizolid phosphate (TZP) for the treatment of MRSA-related ocular and orbital infections. An ionic-gelation method was used to prepare TZP-encapsulated CSNPs using tripolyphosphate-sodium (TPP) as cross-linker. Particle characterization was performed by the DLS technique (Zeta-Sizer), structural morphology was observed by SEM. The drug encapsulation and loading were determined by the indirect method. In-vitro release was conducted through dialysis bags in simulated tear fluid (pH 7) with 0.25% Tween-80. Physicochemical characterizations were performed for ocular suitability of CSNPS. An antimicrobial assay was conducted on different strains of Gram-positive bacteria. Eye-irritation from CSNPs was checked in rabbits. Transcorneal flux and apparent permeability of TZP from CSNPs was estimated through excised rabbit cornea. Ionic interaction between the anionic and cationic functional groups of TPP and CS, respectively, resulted in the formation of CSNPs at varying weight ratios of CS/TPP with magnetic stirring (700 rpm) for 4 h. The CS/TPP weight ratio of 3.11:1 with 10 mg of TZP resulted in optimal-sized CSNPs (129.13 nm) with high encapsulation (82%) and better drug loading (7%). Release profiles indicated 82% of the drug was released from the TZP aqueous suspension (TZP-AqS) within 1 h, while it took 12 h from F2 to release 78% of the drug. Sustained release of TZP from F2 was confirmed by applying different release kinetics models. Linearity in the profile (suggested by Higuchi’s model) indicated the sustained release property CSNPs. F2 has shown significantly increased (p < 0.05) antibacterial activity against some Gram-positive strains including one MRSA strain (SA-6538). F2 exhibited a 2.4-fold increased transcorneal flux and apparent permeation of TZP as compared to TZP-AqS, indicating the better corneal retention. No sign or symptoms of discomfort in the rabbits’ eyes were noted during the irritation test with F2 and blank CSNPs, indicating the non-irritant property of the TZP-CSNPs. Thus, the TZP-loaded CSNPs have strong potential for topical use in the treatment of ocular MRSA infections and related inflammatory conditions.

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for the treatment of advanced HCC; however, the reported response rate to such a therapeutic is suboptimal (<3%). Piperine (PIP) is an alkaloid demonstrated to exert a direct tumoricidal activity in HCC and improve the pharmacokinetic profiles of anticancer drugs including SORA. In this study, we developed a strategy to improve efficacy outcomes in HCC using PIP as an add-on treatment to support the first-line therapy SORA using biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). SORA and PIP (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) and stabilized with various concentrations of polyvinyl alcohol (PVA). The SORA and PIP-loaded PNPs (SP-PNPs) were characterized using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM), Release of these drugs from SP-PNPs was investigated in vitro at both physiological and acidic pH, and kinetic models were employed to assess the mechanism of drug release. The in vitro efficacy of SP-PNPs against HCC cells (HepG2) was also evaluated. FTIR and XRD analyses revealed that the drugs encapsulated in PNPs were in an amorphous state, with no observed chemical interactions among the drugs or excipients. Assessment of drug release in vitro at pH 5 and 7.4 showed that SORA and PIP loaded in PNPs with 0.5 % PVA were released in a sustained manner, unlike pure drugs, which exhibited relatively fast release. SP-PNPs with 0.5 % PVA were spherical, had an average size of 224 nm, and had a high encapsulation efficiency (SORA ∼ 82 %, PIP ∼ 79 %), as well as superior cytotoxicity compared to SORA monotherapy in vitro. These results suggest that combining PIP with SORA using PNPs may be an effective strategy for the treatment of HCC and may set the stage for a comprehensive in vivo study to evaluate the efficacy and safety of this novel formulation using a murine HCC model.

The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (Tgel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. Tgel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a Tgel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS). In-vivo ocular pharmacokinetics indicated a significant improvement in ophthalmic bioavailability of epinephrine (active form of DV). F8 was non-irritant to the eyes and showed a successful, continuous and superior ability to reduce IOP compared to DV-AqS in rabbits. In conclusion, our developed system could be an appropriate substitute to the conventional DV eye preparations in the management of elevated IOP.

Elastin-like polypeptides (ELPs) are being developed for numerous biomedical applications. There is a limited understanding of ELP biocompatibility, with conflicting results in the literature. Protein adsorption is the fate determining event for blood-contacting biomaterials. The aim of this study is to elucidate the biocompatibility of ELP-based nanoparticles by examining the adsorbed proteome from platelet poor human plasma as a function of the physicochemical properties of these nanoparticles: diameter, amino acid hydrophobicity, and chain length. It was found that all ELP constructs had adsorbed an extremely large amount of albumin and high levels of immunoglobulin G and activated complement factor 3. Variations in the compositions of the proteomes across the eight nanoparticle systems studied were observed for plasminogen, fibronectin, activated fibrinogen, and coagulation modulating antithrombin and alpha2 macroglobulin. Plasma clotting experiments showed that ELP-based nanoparticles slightly inhibited normal blood clotting, with shorter and/or more hydrophilic constructs showing a greater difference from the control than longer or more hydrophobic constructs. These results indicate that ELP nanoparticles, regardless of chain length, particle diameter, or amino acid hydrophobicity, may have the potential to stimulate a humoral immune response via immunoglobulin G and activated complement factor 3 despite the large amounts of albumin adsorbed at the blood-material interface.