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1.
Prep Biochem Biotechnol ; 52(1): 99-107, 2022.
Article in English | MEDLINE | ID: mdl-33890844

ABSTRACT

The objective of this study is to synthesize neem-silver nitrate nanoparticles (neem-AgNPs) using aqueous extracts of Azadirachta indica A. Juss for malaria therapy. Neem leaves collected from FRIM Malaysia were authenticated and extracted using Soxhlet extraction method. The extract was introduced to 1 mM of silver nitrate solution for neem-AgNPs synthesis. Synthesized AgNPs were further characterized by ultraviolet-visible spectroscopy and the electron-scanning microscopy. Meanwhile, for the anti-plasmodial activity of the neem-AgNPs, two lab-adapted Plasmodium falciparum strains, 3D7 (chloroquine-sensitive), and W2 (chloroquine-resistant) were tested. Red blood cells hemolysis was monitored to observe the effects of neem-AgNPs on normal and parasitized red blood cells. The synthesized neem-AgNPs were spherical in shape and showed a diameter range from 31-43 nm. When compared to aqueous neem leaves extract, the half inhibitory concentration (IC50) of the synthesized neem-AgNPs showed a four-fold IC50 decrease against both parasite strains with IC50 value of 40.920 µg/mL to 8.815 µg/mL for 3D7, and IC50 value of 98.770 µg/mL to 23.110 µg/mL on W2 strain. The hemolysis assay indicates that the synthesized neem-AgNPs and aqueous extract alone do not have hemolysis activity against normal and parasitized red blood cells. Therefore, this study shows the synthesized neem-AgNPs has a great potential to be used for malaria therapy.


Subject(s)
Antimalarials/chemistry , Azadirachta/chemistry , Plant Extracts/chemistry , Silver Nitrate/chemistry , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Green Chemistry Technology , Humans , Malaria, Falciparum/drug therapy , Nanoparticles/chemistry , Plasmodium falciparum/drug effects , Silver Nitrate/chemical synthesis , Silver Nitrate/pharmacology
2.
Int J Pharm ; 580: 119197, 2020 Apr 30.
Article in English | MEDLINE | ID: mdl-32145339

ABSTRACT

Topical semi-solid formulations are ubiquitous in personal care and pharmaceutical applications. For centuries, these topical formulations have facilitated delivery of active ingredients such as botanical oils, medicinal extracts and more recently antibiotics and biologics. Numerous strategies exist for the stabilization and release of these active ingredients from semi-solid formulations, namely, inclusion of anti-oxidants and surfactants to extend shelf life and facilitate delivery respectively. However, in the instance where the active ingredient itself is an oxidizing agent, traditional strategies for formulation have limited utility. Recent evidence has highlighted the exceptional efficacy and safety of highly oxidizing silver compounds, containing Ag2+ and Ag3+. These higher oxidation states of silver provide antimicrobial and antibiofilm activity without impairing healing. However, as strong oxidizing agents, their application in medical device and pharmaceutical formulations such as semi-solid formulations are limited. The present study reports on the development of a silicone-based gel formulation of silver oxynitrate (Ag7NO11), a higher oxidation state silver complex. In this study the chemical stability of silver oxynitrate was examined through solid state characterization with X-ray diffraction, formulation stability and microstructure of the semi-solid gel evaluated through various rheological techniques, therapeutic functionality of the semi-solid formulation investigated through in-vitro planktonic and biofilm antimicrobial studies, and biocompatibility assessed though in-vitro mammalian fibroblast and in-vivo porcine wound healing models. Enhanced stability of silver oxynitrate within the semi-solid formulation was observed over a four-month X-ray diffraction study. At the end of the study, silver oxynitrate was identified as the principal diffraction pattern in the semi-solid formulation where argentic oxide diffraction peaks were observed to be dominant in silver oxynitrate powders alone. Viscoelastic or gel-like behavior of the formulation was observed under dynamic rheological study where the storage modulus (G' = 1.77 ± 0.02 × 104 Pa) significantly exceeded the loss modulus (G″ = 4.89 ± 3.72 × 102 Pa) (p < 0.0001). No significant (p = 0.84) change was observed in the apparent viscous response within the last three months of the study period indicative that the formulation approached a steady rheological state. The silver oxynitrate semi-solid formulation provided sustained in-vitro antimicrobial activity (>99.99% kill) over seven days with a significant reduction in biofilm within 6 h (p < 0.001). In-vitro mammalian fibroblast studies demonstrated the formulation to be non-cytotoxic and 100% epithelialization was observed within a six-day in-vivo porcine deep partial-thickness wound. The improved chemical stability, biocompatibility and efficacy results indicate that silicone gel semi-solid formulation may be a promising medicinal configuration to facilitate expansion of the clinical use of silver oxynitrate.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Biofilms/drug effects , Drug Compounding/methods , Oxygen/chemistry , Silver Nitrate/chemical synthesis , Administration, Topical , Animals , Anti-Bacterial Agents/administration & dosage , Biofilms/growth & development , Cell Line , Female , Gels , Mice , Microbial Sensitivity Tests/methods , Oxygen/administration & dosage , Silver Nitrate/administration & dosage , Swine , X-Ray Diffraction/methods
3.
J Biosci Bioeng ; 126(1): 44-52, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29496400

ABSTRACT

We examined the effect of various concentrations of HAuCl4, AgNO3, Na2SeO3, Na2SiO3, and GeO2 on mycelial growth of the soil basidiomycetes Agaricus bisporus and A. arvensis in submerged and solid media. Fungal mycelial extracts and cell-free culture filtrates were able to reduce ions of Au, Ag, Se, Si, and Ge compounds, forming Au0, Ag0, Se0, Si0/SiO2 and Ge0/GeO2 nanoparticles. The physical characteristics of the mycogenic nanoparticles differed depending on the species of Agaricus and the type of extract. Au nanospheres obtained with cell-free culture filtrates were of 2-5 nm diameter in A. bisporus and of 2-10 nm in A. arvensis. Nanoparticles produced by extracts of mycelia were several times larger and highly heterogenous. Ag nanoparticles produced by cell-free culture filtrates were spherical or irregular-shaped and agglomerated, whereas with extracts of mycelia, small homogenous nanospheres of 1-10 nm were formed. Se nanospheres obtained with cell-free culture filtrates were of 100-250 nm diameter in A. bisporus and of 150-550 nm diameter in A. arvensis. The particles synthesized with extracts of mycelia were of 40-140 nm in A. bisporus and of 100-250 nm in A. arvensis. Incubation of Na2SiO3 with cell-free culture filtrates resulted in porous Si nanoparticles of 30-65 nm in A. bisporus and of 50-200 nm in A. arvensis. Ge nanoparticles synthesized by both Agaricus species were mostly spheres of 50-250 nm diameter.


Subject(s)
Agaricus/metabolism , Nanoparticles/chemistry , Nanoparticles/metabolism , Agaricus/growth & development , Basidiomycota/metabolism , Germanium/chemistry , Germanium/metabolism , Gold/chemistry , Mycelium/growth & development , Mycelium/metabolism , Selenium Oxides/chemical synthesis , Selenium Oxides/chemistry , Selenium Oxides/metabolism , Silicon/chemistry , Silicon Dioxide/chemical synthesis , Silicon Dioxide/chemistry , Silicon Dioxide/metabolism , Silver/chemistry , Silver Nitrate/chemical synthesis , Silver Nitrate/chemistry , Silver Nitrate/metabolism , Soil , Soil Microbiology
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