Gold nanoparticles from plant extracts and their bioactive compounds to treat various maladies have become an area of interest to many researchers. Acne vulgaris is an inflammatory disease of the pilosebaceous unit caused by the opportunistic bacteria Cutibacterium acnes and Staphylococcus epidermis. These bacteria are not only associated with inflammatory acne but also with prosthetic-implant-associated infections and wounds. Studies have hypothesised that these bacteria have a mutualistic relationship and act as a multispecies system. It is believed that these bacteria form a multispecies biofilm under various conditions and that these biofilms contribute to increased antibiotic resistance compared to single-species biofilms. This study aimed to investigate the antibacterial and wound healing potential of synthesised gold nanoparticles (AuNPs) from an endemic South African plant, Plectranthus aliciae (AuNPPAE), its major compound rosmarinic acid (AuNPRA) and a widely used antibiotic, tetracycline (AuNPTET). Synthesised gold nanoparticles were successfully formed and characterised using ultraviolet–visible spectroscopy (UV–vis), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential (ζ-potential), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED), and they were investigated for stability under various biological conditions. Stable nanoparticles were formed with ζ-potentials of −18.07 ± 0.95 mV (AuNPPAE), −21.5 ± 2.66 mV (AuNPRA), and −39.83 ± 1.6 mV (AuNPTET). The average diameter of the AuNPs was 71.26 ± 0.44 nm, 29.88 ± 3.30 nm, and 132.6 ± 99.5 nm for AuNPPAE, AuNPRA, and AuNPTET, respectively. In vitro, biological studies confirmed that although no antibacterial activity or biofilm inhibition was observed for the nanoparticles tested on the multispecies C. acnes and S. epidermis systems, these samples had potential wound closure activity. Gold nanoparticles formed with rosmarinic acid significantly increased wound closure by 21.4% at 25% v/v (≈29.2 µg/mL) compared to the negative cell control and the rosmarinic acid compound at the highest concentration tested of 500 µg/mL. This study concluded that green synthesised gold nanoparticles of rosmarinic acid could potentially be used for treating wounds.
It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate-specific membrane antigen (PSMA) targeting agents PSMA-11 and PSMA-617, which accumulate in prostate tumours, allow for [ 68 Ga]Ga 3+ -radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [ 68 Ga]Ga-PSMA-617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [ 68 Ga]Ga-PSMA-617-ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [ 68 Ga] Ga-PSMA-617-ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [ 68 Ga]Ga-PSMA-617-ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [ 68 Ga]Ga-PSMA-617-ME occurred at 0.125 mg/mL by HEK293 cells compared with PC3 cells. The biodistribution in wild-type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%). The incorporation of [ 68 Ga]Ga-PSMA-617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means.
Developing nanoparticulate delivery systems that will allow easy movement and localisation of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(D,L-lactide-coglycolide) (PLGA) nanoparticles containing samarium-153 oxide ([ 153 Sm]Sm 2 O 3 ) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive 153 Sm-loaded -PLGA nanoparticles. The nanoparticles were characterized for size, Zeta potential and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The 153 Sm-loaded -PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The Zeta potential ranged between 5 and 20 mV. The [ 153 Sm]Sm 2 O 3 loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles . While the IV injected [ 153 Sm]Sm 2 O 3 loaded PLGA nanoparticles exhibited the highest localisation of nanoparticles in the spleen (8.63%ID/g) and liver (3.07%ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen, From the biodistribution data obtained it is clear that polymeric nano scale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.
The human skin is home to millions of bacteria, fungi, and viruses which form part of a unique microbiome. Commensal microbes, including Cutibacterium acnes can occasionally become opportunistic resulting in the onset of dermatological diseases such as acne. Acne is defined as a chronic inflammatory disorder based on its ability to persist for long periods throughout an individual’s life. The synthesis of gold nanoparticles (AuNPs) was performed using the bottom-up approach by reduction of a gold salt (HAuCl4.3H2O) by the methanol extract (HO-MeOH) and aqueous decoction prepared from the dried aerial parts of Helichrysum odoratissimum (HO-Powder). The HO-MeOH and HO-Powder AuNPs were prepared as unstabilised (−GA) or stabilized (+GA) by the omission or addition of Gum Arabic (GA) as the capping agent. The characterization of the AuNPs was performed using Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), Ultraviolet-Visual spectroscopy (UV-Vis), Thermogravimetric Analysis (TGA), X-Ray Diffraction (XRD) and Zeta-potential. The MBIC50 values for HO-MeOH − GA and HO-MeOH + GA were 1.79 ± 0.78% v/v and 0.22 ± 0.16% v/v, respectively. The HO-Powder AuNPs showed potent inhibition of C. acnes cell adhesion to the 96-well plates. The HO-MeOH − GA and HO-Powder + GA exhibited IC50 of 22.01 ± 6.13% v/v and 11.78 ± 1.78% v/v, respectively. The activity of the AuNPs validated the anti-adhesion activity of the methanol extract in the crude form. The study emphasizes the selectivity of H. odoratissimum AuNPs for the prevention of C. acnes cell adhesion and not antimicrobial activity, which may prevent the emergence of resistant strains of C. acnes through reduced bactericidal or bacteriostatic activity, while targeting mechanisms of pathogenesis.
It has been herein presented that a microemulsion, known to be an effective and safe drug delivery system following intravenous administration, can be loaded with traces of [68Ga]Ga-PSMA-617 without losing its properties or causing toxicity. Following tolerated IV injections the capability of the microemulsion in altering [68Ga]Ga-PSMA-617 distribution was presented at 120 min post injection based on its ex vivo biodistribution results.
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