Biogenic Silver Nanoparticles of Clinacanthus nutans as Antioxidant with Antimicrobial and Cytotoxic Effects.

Silver nanoparticles (AgNPs) previously synthesised using leaf (AgNP-L) and stem (AgNP-S) extracts of Clinacanthus nutans (C. nutans) were tested to evaluate antimicrobial, antioxidant, and cytotoxicity activities. The AgNPs showed good inhibition against bacteria, but not fungi. The inhibition results showed the highest activity against Staphylococcus aureus (S. aureus) with 11.35 mm (AgNP-L) and 11.52 mm (AgNP-S), while the lowest inhibition was against Escherichia coli (E. coli) with 9.22 mm (AgNP-L) and 9.25 mm (AgNP-S) in the disc diffusion method. The same trend of results was noted in the well diffusion method. The IC50 of AgNP-L and AgNP-S in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays was 417.05 µg/mL and 434.60 µg/mL, as well as 304.31 µg/mL and 326.83 µg/mL, respectively. Ferric reducing power (FRAP) assay showed that AgNP-L [872.389 µmol/L Fe(II)] and AgNP-S [612.770 µmol/L Fe(II)] exhibited significantly (p < 0.05) greater antioxidant activities than leaf extract (CNL) [152.260 µmol/L Fe(II)] and stem extract (CNS) [110.445 µmol/L Fe(II)] of C. nutans. The AgNPs were also proven to possess cytotoxic effects on the breast (MCF-7), cervical (HeLa), and colon (HT-29) cancer cells in a dose-dependent manner. AgNP-S and AgNP-L showed significantly (p < 0.05) higher cytotoxicity against MCF-7 (117.43 µg/mL) and HT-29 (78.47 µg/mL), respectively. In conclusion, the biosynthesised AgNPs from aqueous extract leaves and stem of C. nutans have demonstrated promising potential towards antioxidant, antimicrobial, and cytotoxicity activities.

Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy.

PURPOSE: In chemotherapy, oral administration of drug is limited due to lack of drug specificity for localized colon cancer cells. The inability of drugs to differentiate cancer cells from normal cells induces side effects. Colonic targeting with polymeric nanoparticulate drug delivery offers high potential strategies for delivering hydrophobic drugs and fewer side effects to the target site. Disulfide cross-linked polymers have recently acquired high significance due to their potential to degrade in reducing colon conditions while resisting the upper gastrointestinal tract's hostile environment. The goal of this project is, therefore, to develop pH-sensitive and redox-responsive fluorescein-labeled wheat germ agglutinin (fWGA)-mounted disulfide cross-linked alginate nanoparticles (fDTP2) directly targeting docetaxel (DTX) in colon cancer cells. METHODS: fDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29. RESULTS: fDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and -1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC50) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such. CONCLUSION: In short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.

Cytotoxicity of targeted PLGA nanoparticles: a systematic review.

Recent advances in nanotechnology have contributed tremendously to the development and revolutionizing of drug delivery systems in the field of nanomedicine. In particular, targeting nanoparticles based on biodegradable poly(lactic-co-glycolic acid) (PLGA) polymers have gained much interest. However, PLGA nanoparticles remain of concern for their effectiveness against cancer cells and their toxicity to normal cells. The aim of this systematic review is to identify a promising targeting PLGA nanoformulation based on the comparison study of their cytotoxicity potency in different cell lines. A literature search was conducted through the databases of Google Scholar, PubMed, ScienceDirect, Scopus and SpringerLink. The sources studied were published between 2009 and 2019, and a variety of keywords were utilized. In total, 81 manuscripts that met the inclusion and exclusion criteria were selected for analysis based on their cytotoxicity, size, zeta potential, year of publication, type of ligand, active compounds and cell line used. The half maximal inhibitory concentration (IC50) for cytotoxicity was the main measurement in this data extraction, and the SI units were standardized to µg mL-1 for a better view of comparison. This systematic review also identified that cytotoxicity potency was inversely proportional to nanoparticle size. The PLGA nanoparticles predominantly exhibited a size of less than 300 nm and absolute zeta potential ∼20 mV. In conclusion, more comprehensive and critical appraisals of pharmacokinetic, pharmacokinetic, toxicokinetic, in vivo and in vitro tests are required for the investigation of the full value of targeting PLGA nanoparticles for cancer treatment.

Redox-Sensitive Linear and Cross-Linked Cystamine-Based Polymers for Colon-Targeted Drug Delivery: Design, Synthesis, and Characterisation.

Cystamine-based polymers may help to achieve controlled and targeted drug delivery to the colon due to their susceptibility to breakage of the disulfide linkage in the low redox potential environment of the colon. In this study, two linear cystamine-based polymers with similar repeating units (LP1 and LP2) and a cross-linked cystamine-based polymer (BP) were synthesised and their kinetics and the various physical conditions underlying cystamine-based polymerisation were evaluated. In brief, N1, N6-bis(2-(tritylthio)ethyl)adipamide (2) was synthesised from the reaction of triphenylmethanol and cysteamine. Next, the trityl group of 2 was removed with trifluoroacetic acid and triethylsilane before proceeding to oxidative polymerisation of the end product, N1, N6-bis(2-mercaptoethyl)adipamide (3) to LP1. The Schotten-Bauman reaction was applied to synthesise LP2 and BP from the reaction of cystamine with adipoyl chloride or trimesoyl chloride. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and mapping showed that oxygen, nitrogen, sulfur, and carbon were homogenously distributed in the polymers, with LP2 and BP having less porous morphologies compared to LP1. Results of zinc-acetic acid reduction showed that all polymers began to reduce after 15 min. Moreover, all synthesised polymers resisted stomach and small intestine conditions and only degraded in the presence of bacteria in the colon environment. Thus, these polymers have great potential for drug delivery applications. LP2 and BP, which were synthesised using the Schotten-Bauman reaction, were more promising than LP1 for colon-targeted drug delivery.

Biocompatible Nutmeg Oil-Loaded Nanoemulsion as Phyto-Repellent.

Plant essential oils are widely used in perfumes and insect repellent products. However, due to the high volatility of the constituents in essential oils, their efficacy as a repellent product is less effective than that of synthetic compounds. Using a nanoemulsion as a carrier is one way to overcome this disadvantage of essential oils. Nutmeg oil-loaded nanoemulsion (NT) was prepared using a high speed homogenizer and sonicator with varying amounts of surfactant, glycerol, and distilled water. Using a phase diagram, different formulations were tested for their droplet size and insect repellent activity. The nanoemulsion containing 6.25% surfactant and 91.25% glycerol (NT 6) had the highest percentage of protection (87.81%) in terms of repellent activity among the formulations tested for the 8 h duration of the experiment. The droplet size of NT 6 was 217.4 nm, and its polydispersity index (PDI) was 0.248. The zeta potential value was -44.2 mV, and the viscosity was 2.49 Pa.s at pH 5.6. The in vitro release profile was 71.5%. When the cytotoxicity of NT 6 at 400 µg/mL was tested using the MTS assay, cell viability was 97.38%. Physical appearance and stability of the nanoemulsion improved with the addition of glycerol as a co-solvent. In summary, a nutmeg oil-loaded nanoemulsion was successfully formulated and its controlled release of the essential oil showed mosquito repellent activity, thus eliminating the disadvantages of essential oils.

Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery.

In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1-5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1-5) under sonication. DTX was successfully loaded into the resulting MP1-5 to form DTX-loaded nanoparticles (DMP1-5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of -2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.

Biocompatible disulphide cross-linked sodium alginate derivative nanoparticles for oral colon-targeted drug delivery.

The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colon-specific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteamine-based disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential= -58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 µg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery.

Cytotoxicity of Plant-Mediated Synthesis of Metallic Nanoparticles: A Systematic Review.

In the field of medicine, nanomaterials, especially those derived using the green method, offer promise as anti-cancer agents and drug carriers. However, the biosafety of metallic nanoparticles used as anti-cancer agents remains a concern. The goal of this systematic review was to compare the cytotoxicity of different plant-mediated syntheses of metallic nanoparticles based on their potency, therapeutic index, and cancer cell type susceptibility in the hopes of identifying the most promising anti-cancer agents. A literature search of electronic databases including Science Direct, PubMed, Springer Link, Google Scholar, and ResearchGate, was conducted to obtain research articles. Keywords such as biosynthesis, plant synthesis, plant-mediated, metallic nanoparticle, cytotoxicity, and anticancer were used in the literature search. All types of research materials that met the inclusion criteria were included in the study regardless of whether the results were positive, negative, or null. The therapeutic index was used as a safety measure for the studied compound of interest. Data from 76 selected articles were extracted and synthesised. Seventy-two studies reported that the cytotoxicity of plant-mediated synthesis of metallic nanoparticles was time and/or dose-dependent. Biosynthesised silver nanoparticles demonstrated higher cytotoxicity potency compared to gold nanoparticles synthesised by the same plants (Plumbago zeylanica, Commelina nudiflora, and Cassia auriculata) irrespective of the cancer cell type tested. This review also identified a correlation between the nanoparticle size and morphology with the potency of cytotoxicity. Cytotoxicity was found to be inversely proportional to nanoparticle size. The plant-mediated syntheses of metallic nanoparticles were predominantly spherical or quasi-spherical, with the median lethal dose of 1⁻20 µg/mL. Nanoparticles with other shapes (triangular, hexagonal, and rods) were less potent. Metallic nanoparticles synthesised by Abutilon inducum, Butea monosperma, Gossypium hirsutum, Indoneesiella echioides, and Melia azedarach were acceptably safe as anti-cancer agents, as they had a therapeutic index of >2.0 when tested on both cancer cells and normal human cells. Most plant-mediated syntheses of metallic nanoparticles were found to be cytotoxic, although some were non-cytotoxic. The results from this study suggest a focus on a selected list of potential anti-cancer agents for further investigations of their pharmacodynamic/toxicodynamic and pharmacokinetic/toxicokinetic actions with the goal of reducing the Global Burden of Diseases and the second leading cause of mortality.