Development and Antibacterial Investigation of Linezolid-Loaded SPIONs and HPLC Method Development for Quantitative Analysis of Linezolid.

BACKGROUND: Linezolid (LNZ) is extremely prone to resistance. The development of resistance to LNZ should be taken into consideration when selecting this drug as a therapeutic option. It is well established that reactive oxygen species (ROS) generated by iron oxide nanoparticles (MNPs) could kill the infecting bacteria. So, we hypothesized the synergistic antibacterial effect of iron oxide nanoparticles and LNZ. OBJECTIVE: To study the release and antibacterial effects of LNZ-loaded superparamagnetic iron oxide nanoparticles (SPIONs) on Staphylococcus aureus and Streptococcus pneumoniae. METHOD: Ferrofluid containing SPIONs was synthesized via chemical co-precipitation method and stabilized by sodium lauryl sulphate (SLS). SPIONs were then loaded with LNZ and characterized for particle size, FT-IR, XRD, and entrapment efficiency. Further antibacterial activity of SPIONs and LNZ-loaded SPIONs was investigated. For the in vitro release findings, HPLC analytical method development and validation were performed. RESULTS: Isolation of LNZ was accomplished on a C-18 column with methanol-TBHS (tetra butyl ammonium hydrogen sulphate, 50:50, v/v). The eluate was monitored at 247 nm with a retention time of 4.175 min. The MNP's DLS measurement revealed monodispersed particles with an average size of 16.81 ± 1.07 nm and PDI 0.176 ± 0.012. In optimized formulation, 25 ± 1.75% (w/w) of the drug was found to be entrapped. XRD revealed uniform coating of oleic acid covering the entire magnetic particles' surface with no change in its crystallinity. An effective antimicrobial activity was observed at the lowered dose of drug. CONCLUSIONS: A robust HPLC method was developed to quantify the LNZ in MNPs, and outcomes showed that the reduced dose of LNZ incorporated in SPIONs was able to show similar activity as the marketed product. HIGHLIGHTS: Successfully reduction of the dose of LNZ was established with the aid of biocompatible MNPs to attain the equivalent antibacterial activity.

Doxorubicin loaded carboxymethyl Assam bora rice starch coated superparamagnetic iron oxide nanoparticles as potential antitumor cargo.

In recent years, polysaccharide-decorated superparamagnetic iron oxide nanoparticles (SPIONs) have gained attention in the field of "nanotheranostics" with integrated diagnostic and therapeutic functions. Carboxymethyl Assam bora rice starch-stabilized SPIONs (CM-ABRS SPIONs), synthesized by co-precipitation method, has already shown exciting potential towards magnetic drug targeting potential. After establishing it as a promisable targeting carrier, the present study is focused on the next step i.e. to evaluate its In vitro anti-tumor potential by loading anticancer drug "Doxorubicin hydrochloride (DOX)" onto CM-ABRS SPIONs. DOX-loaded CM-ABRS SPIONs were physico-chemically characterized by DLS, zeta-potential, TEM, FT-IR, XRD, and VSM analysis. Spectroflourimetric analysis confirmed the maximum loading of DOX up to 6% (w/w) onto CM-ABRS SPIONs via electrostatic interactions. Further, molecular level drug performance was investigated by docking study against receptors (HER-2 and Folate receptor-α) over expressed in cancer cells and MTT assay (in MCF-7 and HeLa cell line), which conferred promisable results of DOX-CM-ABRS SPIONs as compared to standard DOX solution.

Carboxymethyl Assam Bora rice starch coated SPIONs: Synthesis, characterization and in vitro localization in a micro capillary for simulating a targeted drug delivery system.

Carboxymethyl Assam Bora rice starch coated superparamagnetic iron oxide nanoparticles (CM-ABRS SPIONs) were chemically synthesized by co-precipitation method and particle size reduction was controlled by high energy homogenization process. Effects of various process variables (polymer concentration, homogenization speed and cycles) were optimized on the basis of average particle size (Z-average) and polydispersity index (PDI) of CM-ABRS SPIONs. The optimized CM-ABRS SPIONs were characterized for their particle size, surface morphology, electrokinetic potential, chemical interactions, crystallinity, magnetic properties, and targeting potential in presence of external magnetic field. In vitro localization of CM-ABRS SPIONs in a suspension of FITC (Fluorescein isothiocyanate) labeled RBCs (Red blood cells; hematocrit value; 45% (v/v)) was conducted inside a square glass capillary (500 × 500 µm2 cross section) in the presence of an externally applied magnetic field (Ms = 150 mT), simulating the case of magnetic drug targeting (MDT) approach. The aggregation dynamics of CM-ABRS SPIONs inside a micro capillary was observed with respect to time (t = 0 to 600 s), which shows proportionality to time of exposure to the externally applied magnetic field. This in vitro study acts as an important platform for design and optimization of active targeted drug delivery system.

Chondroitin sulfate-capped super-paramagnetic iron oxide nanoparticles as potential carriers of doxorubicin hydrochloride.

Chondroitin-4-sulfate (CS), a glycosaminoglycan, was used to prepare CS-capped super-paramagnetic iron oxide nanoparticles, which were further employed for loading a water-soluble chemotherapeutic agent (doxorubicin hydrochloride, DOX). CS-capped SPIONs have potential biomedical application in cancer targeting. The optimized formulation had a hydrodynamic size of 91.2±0.8nm (PDI; 0.228±0.004) and zeta potential of -49.1±1.66mV. DOX was loaded onto the formulation up to 2% (w/w) by physical interaction with CS. TEM showed nano-sized particles having a core-shell structure. XRD confirmed crystal phase of iron oxide. FT-IR conceived the interaction of iron oxide with CS as bidentate chelation and also confirmed DOX loading. Vibration sample magnetometry confirmed super-paramagnetic nature of nanoparticles, with saturation magnetization of 0.238emug(-1). In vitro release profile at pH 7.4 showed that 96.67% of DOX was released within 24h (first order kinetics). MTT assay in MCF7 cells showed significantly higher (p<0.0001) cytotoxicity for DOX in SPIONs than DOX solution (IC50 values 6.294±0.4169 and 11.316±0.1102µgmL(-1), respectively).

Synthesis and in vitro localization study of curcumin-loaded SPIONs in a micro capillary for simulating a targeted drug delivery system.

Nano-sized curcumin-loaded super-paramagnetic iron oxide nanoparticles (CUR-OA-SPIONs) were synthesized chemically by co-precipitation method using oleic acid as a stabilizer and Myrj 52 as a surfactant. The synthesized nanoparticles were characterized for their shape, size, surface morphology, electrokinetic potential, magnetic properties, crystalinity, chemical interactions and thermal transitions. The synthesized CUR-OA-SPIONs were spherical, mono-dispersed, physically stable and super-paramagnetic in nature. In vitro localization study and aggregation dynamics of CUR-OA-SPIONs were studied with a flow of blood inside a square glass capillary (500×500 µm(2) cross section) in the presence of an externally applied magnetic field (Ms=1200 mT). This research which is first of its kind showed the fluorescent imaging of CUR-OA-SPIONs with respect to time to understand the aggregation dynamics of magnetic nanoparticles in a micro capillary simulating the case of targeted drug delivery system. The size of the aggregation increases with respect to time (t=0(+)s to t=500 s), while no significant change in the size of the aggregate was observed after time t=500 s.