Magnetoelectric core-shell CoFe2O4@BaTiO3 nanorods: their role in drug delivery and effect on multidrug resistance pump activity in vitro.

Nanoparticle mediated targeted drug delivery has become a widespread area of cancer research to address premature drug delivery problems. We report the synthesis of magneto-electric (ME) core-shell cobalt ferrite-barium titanate nanorods (CFO@BTO NRs) to achieve "on demand" drug release in vitro. Physical characterizations confirmed the formation of pure CFO@BTO NRs with appropriate magnetic and ferroelectric response, favorable for an externally controlled drug delivery system. Functionalization of NRs with doxorubicin (DOX) and methotrexate (MTX) achieved up to 98% drug release in 20 minutes, under a 4 mT magnetic field (MF). We observed strong MF and dose dependent cytotoxic response in HepG2 and HT144 cells and 3D spheroid models (p < 0.05). Cytotoxicity was characterized by enhanced oxidative stress, causing p53 mediated cell cycle arrest, DNA damage and cellular apoptosis via downregulation of Bcl-2 expression. In addition, MF and dose dependent inhibition of Multidrug Resistance (MDR) pump activity was also observed (p < 0.05) indicating effectivity in chemo-resistant cancers. Hence, CFO@BTO NRs represent an efficient carrier system for controlled drug delivery in cancer nanotherapeutics, where higher drug uptake is a prerequisite for effective treatment.

GC-MS Analysis and Various In Vitro and In Vivo Pharmacological Potential of Habenaria plantaginea Lindl.

Background. The current study aims to give a scientific origin for employing Habenaria plantaginea Lindl. as a potential candidate against nociception, inflammation, and pyrexia. The pharmacological studies were performed on crude extract and subfractions. In the gas chromatography-mass spectroscopy analysis, a total of 21 compounds were identified. The plant samples were displayed for in vitro anti-inflammatory potentials. The observed IC50 for chloroform against cyclooxygenase-2 and 5-lipoxygenase enzymes was 33.81 and 26.74 µg/mL, respectively. The in vivo activities were prerequisites with the acute toxicity studies. In carrageenan-induced inflammation, the chloroform fraction exhibited 46.15% inhibition similar to that of standard drug diclofenac sodium 47.15%. Likewise, in the acetic acid-induced writhing test, the ethyl acetate fraction displayed 71.42% activity, which was dose-dependent as that of standard drug. In Brewer's yeast-induced antipyretic activity, a significant decrease in rectal volume was observed after 30, 60, and 90 minutes. Moreover, the results of this study indicated that the chloroform and ethyl acetate fractions inhibited nociception, inflammation, and pyrexia dose dependently. Likewise, mechanistic insights indicated that naloxone antagonized the antinociceptive effect of chloroform and ethyl acetate fractions, thereby signifying the involvement of opioidergic mechanisms respectively. These results suggest that these molecules present in this plant have synergistically beneficial potential for the cure and management of analgesia, inflammation, and pyrexia.

Phytochemical analysis and versatile in vitro evaluation of antimicrobial, cytotoxic and enzyme inhibition potential of different extracts of traditionally used Aquilegia pubiflora Wall. Ex Royle.

BACKGROUND: Himalayan Columbine (Aquilegia pubiflora Wall. Ex Royle) is a medicinal plant and have been used as traditional treatments for various human diseases including skin burns, jaundice, hepatitis, wound healing, cardiovascular and circulatory diseases. Till now there is no report available on phytochemical investigation of Himalayan Columbine and to the best of our knowledge, through present study we have reported for the first time, the phytochemical analysis and pharmacological potentials of different leaf extracts of Aquilegia pubiflora. METHODS: Four types of extracts were prepared using solvent of different polarities (Distilled water APDW, Methanol APM, Ethanol APE and Ethyl acetate APEA), and were evaluated to determine the best candidate for potent bioactivity. Phytochemical constituents in prepared extracts were quantified through HPLC analysis. Subsequently, all four types of leaf extracts were then evaluated for their potential bioactivities including antimicrobial, protein kinase inhibition, anti-inflammatory, anti-diabetic, antioxidant, anti-Alzheimer, anti-aging and cytotoxic effect. RESULTS: HPLC analysis demonstrated the presence of dvitexin, isovitexin, orientin, isoorientin, ferulic acid, sinapic acid and chlorogenic acid in varied proportions in all plant extracts. Antimicrobial studies showed that, K. pneumonia was found to be most susceptible to inhibition zones of 11.2 ± 0.47, 13.9 ± 0.33, 12.7 ± 0.41, and 13.5 ± 0.62 measured at 5 mg/mL for APDW, APM, APE and APEA respectively. A. niger was the most susceptible strain in case of APDW with the highest zone of inhibition 14.3 ± 0.32, 13.2 ± 0.41 in case of APM, 13.7 ± 0.39 for APE while 15.4 ± 0.43 zone of inhibition was recorded in case of APEA at 5 mg/mL. The highest antioxidant activity of 92.6 ± 1.8 µgAAE/mg, 89.2 ± 2.4 µgAAE/mg, 277.5 ± 2.9 µM, 289.9 ± 1.74 µM for TAC, TRP, ABTS and FRAP, respectively, was shown by APE. APM, APE and APEA extracts showed a significant % cell inhibition (above 40%) against HepG2 cells. The highest anti-inflammatory of the samples was shown by APE (52.5 ± 1.1) against sPLA2, (41.2 ± 0.8) against 15-LOX, followed by (38.5 ± 1.5) and (32.4 ± 0.8) against COX-1 and COX-2, respectively. CONCLUSIONS: Strong antimicrobial, Protein Kinase potency and considerable α-glucosidase, α-amylase, and cytotoxic potential were exhibited by plant samples. Significant anti-Alzheimer, anti-inflammatory, anti-aging, and kinase inhibitory potential of each plant sample thus aware us for further detailed research to determine novel drugs.

Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles.

In this study, poly(isobutylene-alt-maleic anhydride) (PMA)-coated spinel ferrite (MFe2O4, where M = Fe, Co, Ni, or Zn) nanoparticles (NPs) were developed as carriers of the anticancer drugs doxorubicin (DOX) and methotrexate (MTX). Physical characterizations confirmed the formation of pure cubic structures (14-22 nm) with magnetic properties. Drug-loaded NPs exhibited tumor specificity with significantly higher (p < 0.005) drug release in an acidic environment (pH 5.5). The nanoparticles were highly colloidal (zeta potential = -35 to -26 mV) in deionized water, phosphate buffer saline (PBS), and sodium borate buffer (SBB). They showed elevated and dose-dependent cytotoxicity in vitro compared to free drug controls. The IC50 values ranged from 0.81 to 3.97 µg/mL for HepG2 and HT144 cells, whereas IC50 values for normal lymphocytes were 10 to 35 times higher (18.35-43.04 µg/mL). Cobalt ferrite (CFO) and zinc ferrite (ZFO) NPs were highly genotoxic (p < 0.05) in cancer cell lines. The nanoparticles caused cytotoxicity via oxidative stress, causing DNA damage and activation of p53-mediated cell cycle arrest (significantly elevated expression, p < 0.005, majorly G1 and G2/M arrest) and apoptosis. Cytotoxicity testing in 3D spheroids showed significant (p < 0.05) reduction in spheroid diameter and up to 74 ± 8.9% of cell death after two weeks. In addition, they also inhibited multidrug resistance (MDR) pump activity in both cell lines suggesting effectivity in MDR cancers. Among the tested MFe2O4 NPs, CFO nanocarriers were the most favorable for targeted cancer therapy due to excellent magnetic, colloidal, cytotoxic, and biocompatible aspects. However, detailed mechanistic, in vivo cytotoxicity, and magnetic-field-assisted studies are required to fully exploit these nanocarriers in therapeutic applications.

Field-controlled magnetoelectric core-shell CoFe2O4@BaTiO3 nanoparticles as effective drug carriers and drug release in vitro.

The targeted drug release at tumor cells while sparing normal cells is a huge challenge. Core-shell magnetoelectric (ME) nanoparticles have addressed this problem using shape-dependent magneto-electric attributes. The colloidally stable, core-shell cobalt ferrite@barium titanate (CFO@BTO) ME nanoparticles (NPs) used for in vitro study were synthesized using sonochemical method. The structural characteristics and core-shell morphology were analyzed by X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) respectively. Further magnetic and exchange coupling between two phases of ME nanostructures were studied at room temperature. Colloidal stability was studied in different suspension solutions (Water, SBB, PBS, and DMEM) using dynamic light scattering. Subsequently, the synthesized nanoparticles were functionalized with anticancer drugs including doxorubicin and methotrexate up to 80% via (EDC) chemistry. In vitro cytotoxicity studies carried out on human hepatocellular carcinoma (HepG2) and human malignant melanoma (HT144), cells validated the magneto-electric property of CFO@BTO nano-carriers in the presence of external magnetic field (5 mT), with significantly enhanced cytotoxicity when compared to free drugs and without field replicates. The resulted IC50 values ranging from 5.3-7.3 µg/ml compared to 30.1-43.1 µg/ml in the absence of a magnetic field also confirmed the involved physical attributes of magnetoelectric nanostructures. The fluorescent microscopy results also indicated the increased apoptosis in magnetic field-assisted samples. Finally, hemolysis assay indicated the suitability of CFO@BTO nano-carriers for intravenous applications at IC50 concentration.

Green and chemically synthesized zinc oxide nanoparticles: effects on in-vitro seedlings and callus cultures of Silybum marianum and evaluation of their antimicrobial and anticancer potential.

Zinc oxide nanoparticles (ZnO-NPs) have been produced by physical and chemical methods. Here, the comparative evaluation of both chemically-synthesised ZnO-NPs (C-ZNPs) and in-vitro cultured S. marianum mediated green-synthesised ZnO-NPs (G-ZNPs) were investigated on seed germination frequency, root and shoot growth, callus induction and biochemical profile of medicinally important plant Silybum marianum. Of all the treatments, callus-mediated ZnO-NPs gave optimum results for seed germination (65%), plantlet's root length (4.3 cm), shoot length (5.3 cm) and fresh and dry weights (220.4 g L-1 and 21.23 g L-1, respectively). Similarly, the accumulation of phenolic (12.3 µg/mg DW) and flavonoid (2.8 µg/mg DW) contents were also enhanced in callus cultures treated with G-ZNPs. We also observed maximum antioxidant activity (99%) in callus cultures treated with G-ZNPs, however, in case of plantlets, these activities were found highest for in-vitro whole plant-mediated ZnO-NPs. Moreover, G-ZNPs also enhanced total protein content (265.32 BSAE/20g FW) in callus cultures. G-ZNPs were further assessed for their effects on several multidrug resistant bacterial strains and human liver carcinoma (HepG2) cells and our findings revealed that callus extracts treated with G-ZNPs show ameliorated antibacterial (highest zone of inhibition (19 mm) against Klebsiella pneumonia) and anticancer (highest cytotoxicity of 64%) activities.

Papaver somniferum L. mediated novel bioinspired lead oxide (PbO) and iron oxide (Fe2O3) nanoparticles: In-vitro biological applications, biocompatibility and their potential towards HepG2 cell line.

To overcome the disadvantages of chemical and physical methods, phyto-fabricated nanoparticles attained great attention due to their multifarious applications. Here we successfully demonstrated Papaver somniferum L. mediated green synthesis of lead oxide (PbO) and iron oxide (Fe2O3) nanoparticles. Characterization of nanoparticles involved techniques including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and energy dispersive X-ray (EDX) associated with scanning electron microscopy (SEM). XRD analysis confirmed the phase identification and crystalline nature. FTIR analysis confirmed the capping of nanoparticles by plants' phytochemicals. SEM revealed morphological features of PbO and Fe2O3 with size of nanoparticles being 23 ±â€¯11 nm and 38 ±â€¯13 nm, respectively. The elemental composition of the nanoparticles was confirmed by EDX. Both bacterial and fungal isolates showed susceptibility towards PbO and Fe2O3 NPs. Both the NPs also showed considerable total antioxidant potential, free radical scavenging potential and reducing power. Insignificant level of α-amylase for both NPs was observed. Fe2O3 NPs showed superior biocompatibility with human RBCs as compared to PbO whereas PbO showed more potent anti-cancer activity as compared to Fe2O3 NPs. Overall our study concluded that both NPs played vital role in multiple biological assays however, extensive research focused on cytotoxic evaluation of NPs in-vivo is required.

Natural products as reservoirs of novel therapeutic agents.

Since ancient times, natural products from plants, animals, microbial and marine sources have been exploited for treatment of several diseases. The knowledge of our ancestors is the base of modern drug discovery process. However, due to the presence of extensive biodiversity in natural sources, the percentage of secondary metabolites screened for bioactivity is low. This review aims to provide a brief overview of historically significant natural therapeutic agents along with some current potential drug candidates. It will also provide an insight into pros and cons of natural product discovery and how development of recent approaches has answered the challenges associated with it.

Exploiting in vitro potential and characterization of surface modified Zinc oxide nanoparticles of Isodon rugosus extract: Their clinical potential towards HepG2 cell line and human pathogenic bacteria.

Little is known about biogenically synthesized Zinc oxide nanoparticles (ZnONPs) from Isodon rugosus. Synthesis of metal oxide NPs from essential oil producing medicinal plants results in less harmful side effects to the human population as compared to chemically synthesized NPs. In this article, we report biogenic synthesis of ZnONPs from in vitro derived plantlets and thidiazuron (TDZ) induced callus culture of Isodon rugosus. Synthesized NPs were characterized using UV-spectra, XRD, FTIR, SEM and EDX. Furthermore, the NPs were evaluated for their potential cytotoxic (against HepG2 cell line) and antimicrobial (against drug resistant Staphylococcus epidermidis, Bacillus subtilis, Klebsiella pneumoniae and Pseudomonas aeruginosa) activities. Pure crystalline ZnONPs with hexagonal and triangular shapes were obtained as a result of callus extract (CE) and whole plant extract (WPE), respectively. ZnONPs showed potent cytotoxic and antimicrobial potential. The antimicrobial and cytotoxic activities of ZnONPs were found to be shape and surface bound phytochemicals dependent. CE mediated hexagonal ZnONPs showed superior anti-cancer and antimicrobial activities as compared to WPE mediated triangular shaped ZnONPs. It is concluded that biogenic ZnONPs have incredible potential as theranostic agents and can be adopted as useful drug delivery system in next generation treatment strategies.