Chitosan-coated liposomes of Carissa spinarum extract: synthesis, analysis and antipneumococcal potency

In the present study, a chitosan-coatedCarissa spinarum-polyphenol-loaded liposome (LipCsP-chitosan) nanocarrierwas fabricated for the delivery ofC. spinarumpolyphenols (CsPs) to improve the bioavailability andantipneumococcal potential of CsPs againstKlebsiella pneumoniae. LipCsP-chitosan was synthesized using the iongelation method and characterized by using a Malvern Zetasizer and Fourier transform infrared (FTIR) spectroscopy.CsP encapsulation and release kinetics were investigated. The antipneumococcal activity of the nanoformulationswas assessed using agar-well diffusion and microdilution assays. LipCsP-chitosan exhibited a hydrodynamic size anda zeta potential of 365.22 ± 0.70 nm and +39.30 ± 0.61 mV, respectively. The encapsulation efficiency of LipCsP-chitosan was 81.5%. FTIR analysis revealed interactions of the liposomes with chitosan and CsPs. A biphasic CsPrelease profile followed by a sustained-release pattern was observed. LipCsP-chitosan presented a higherbioaccessibility of polyphenols in the simulated gastric phase (74.1 ± 1.3%) than in the simulated intestinal phase(63.32 ± 1.00%). LipCsP-chitosan had a relative inhibition zone diameter of 84.33 ± 2.51% when compared with CsPs.At a minimum inhibitory concentration of 31.25 mg/ml, LipCsP-chitosan reduced the viability ofK. pneumoniaeby57.45 ± 3.76% after 24 h. The results obtained from this study offer a new approach to the utilization of LipCsP-chitosan as nanocarriers for candidate antipneumococcal agents

Development of a receptor targeted nanotherapy using a proapoptotic peptide

Philosophiae Doctor - PhDThe prevalence of obesity amongst South Africans is alarming, with more than 29% of men and 56% of women considered to be obese. Angiogenesis, a process for development of new blood vessels play a major role in growth and survival of the adipose tissues. Pharmacological inhibitors of angiogenesis are therefore a sensible strategy to reduce excess body weight. Current anti-obesity drugs have limitations because of their lack of selectivity and specificity, which lead to undesirable side effects and reduced drug efficacy. Future anti-obesity therapeutic strategies should be target-specific, with minimal toxicity towards healthy tissues will be more appropriate for obesity treatment. Targeted nano-therapeutic agents are currently being developed to overcome the drawbacks associated with conventional drug therapies. The nano-based delivery vehicles that specifically target diseased cells are appealing as they could reduce drug toxicity towards healthy tissues and be more effective at lower dosages. The main aim of this study was to develop a receptor-mediated nanotherapy that specifically targets the white adipose tissue vasculature and trigger the death of these cells through apoptosis. The 14 nm gold nanoparticles (AuNPs) were synthesized using theTurkevich method following reduction of gold aurate by sodium citrate salt. Different chemistries were used to functionalise the AuNPs for biological application by conjugating with either vascular targeting peptide or pro-apoptotic peptide on their surface or both. The nanomaterials were characterised by UV-Vis, Zeta potential and transmission electron microscopy (TEM). The sensitivity and specificity of various AuNP conjugates were tested in vitro on colon and breast cancer cell lines. A human (Caco-2) cell line that expresses the receptor for the adipose homing peptide was chosen as an in vitro model system. Cellular toxicity and uptake of the nanoparticles was evaluated using the WST-1 assay, Inductively Coupled Plasma-Optical Emission Spectra (ICP-OES) and TEM. The induction of apoptosis following exposure to the nanoparticles was examined by Western blot and flow cytometric analysis. The anti-proliferative activity of the targeted therapeutic nanoparticles on the cells was more pronounced on the cells expressing the receptor for the adipose homing peptide. The uptake of unfunctionalised AuNPs was higher compared to functionalised nanoparticles, but this did not impair cell viability. The activity of the therapeutic peptide was retained and enhanced following conjugation to AuNPs as shown by Western blot and flow cytometric analysis. The nanotherapy under study demonstrated receptor mediated targeting, and enhanced activity on the cells expressing the receptor. However, the therapeutic and efficacy of the targeted nanotherapy still need to be tested in animal models of obesity to confirm the treatment specificity

Differentially expressed serum proteins from obese Wistar rats as a risk factor for obesity-induced diseases

Obesity is a chronic disease that negatively affects life expectancy through its association with life-threatening diseases such as cancer and cardiovascular diseases. Expression proteomics combined with in silico interaction studies are used to uncover potential biomarkers and the pathways that promote obesity-related complications. These biomarkers can either aid in the development of personalized therapies or identify individuals at risk of developing obesity-related diseases. To determine the serum protein changes, Wistar rats were fed standard chow (low fat, LF), or chow formulated high fat (HF) diets (HF1, HF2 and HF3) for 8 and 42 weeks to induce obesity. Serum samples were collected from lean and obese rats at these time points

Enhanced anti-bacterial activity of biogenic silver nanoparticles synthesized from terminalia mantaly extracts

The global increase in outbreaks and mortality rates associated with multidrug- resistant (MDR) bacteria is a major health concern and calls for alternative treatments. Natural-derived products have shown potential in combating the most dreadful diseases, and therefore serve as an effective source of bioactive compounds that can be used as antibacterial agents. These compounds are able to reduce metal ions and cap nanoparticles to form biogenic nanoparticles (NPs) with remarkable anti-bacterial activities. This study explores the use of Terminalia mantaly (TM) extracts for the synthesis of biogenic silver NPs (TM-AgNPs) and the evaluation of their antibacterial activity. TM-AgNPs were synthetized by the reduction of AgNO3 with aqueous andmethanolic TM extracts. UV–visible (UV-vis) spectrophotometry, Dynamic Light Scattering (DLS), Transmission Electron Microscopy, and Fourier Transform Infrared (FTIR) analyses were used to characterise the TM-AgNPs. Anti-bacterial activity of the TM extracts and TM-AgNPs was evaluated against eight bacterial strains using the broth microdilution assay

Design and synthesis of acyldepsipeptide-1 analogues: antibacterial activity and cytotoxicity screening

Acyldepsipeptides (ADEPs) are receiving more attention as prospective antimicrobial agents due to their unique mode of action and chemical properties. However, their therapeutic potential is limited by their poor pharmacokinetic properties. Chemical modifications have been successful in improving the biocompatibility and bioavailability of ADEPs. In the current study, ADEP1 was modified by introducing a disulphide linkage, replacement of the octa-2,4,6-trienoic acid (OTEA) with either adamantane (Ada) or palmitic acid (Pal), and lastly, comparing the use of D versus L amino acids. The antibacterial effects of the ADEP1 analogues were investigated in Gram-positive and Gram-negative strains using agar well diffusion and microdilution assays. Cytotoxicity was evaluated in human embryonic kidney (HEK)-293 and colon cancer (Caco-2) cells by the MTS assay. Using solid phase peptide synthesis (SPPS), the percentage yield of the synthetic peptides was increased to > 37% with > 96% purity

Encapsulation of variabilin in stearic acid solid lipid nanoparticles enhances its anticancer activity in vitro

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 µM vs. 8.94 µM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 µM for variabilin, Var-SLN and Ceramide, respectively

Green synthesized saunps as a potential delivery platform for cytotoxic alkaloids

The use of natural products as chemotherapeutic agents is well established. However, many are associated with undesirable side effects, including high toxicity and instability. Previous reports on the cytotoxic activity of pyrroloiminoquinones isolated from Latrunculid sponges against cancer cell lines revealed extraordinary activity at IC50 of 77nM for discorhabdins. Their general lack of selectivity against the cancer and normal cell lines, however, precludes further development. In this study, extraction of a South African Latrunculid sponge produced three known pyrroloiminoquinone metabolites (14-bromodiscorhabdin C (5), Tsitsikammamine A (6) and B (7)). The assignment of the structures was established using standard 1D and 2D NMR experiments. To mitigate the lack of selectivity, the compounds were loaded onto gold nanoparticles synthesized using the aqueous extract of a brown seaweed, Sargassum incisifolium (sAuNPs). The cytotoxicity of the metabolites alone, and their sAuNP conjugates, were evaluated together with the known anticancer agent doxorubicin and its AuNP conjugate. The compound-AuNP conjugates retained their strong cytotoxic activity against the MCF-7 cell line, with >90% of the pyrroloiminoquinone-loaded AuNPs penetrating the cell membrane

Antimicrobial effects of gum Arabic-silver nanoparticles against oral pathogens

Dental caries is considered one of the most prevalent oral diseases worldwide, with a high rate of morbidity among populations. It is a chronic infectious disease with a multifactorial etiology that leads to the destruction of the dental tissues. Due to their antimicrobial, anti-inflammatory, antifungal, and antioxidant properties; silver nanoparticles (AgNPs) are incorporated in dental products to help prevent infectious oral diseases. In this study, the antimicrobial efects of AgNPs synthesized using Gum Arabic extracts (GAE) were examined. Te GA-AgNPs were synthesized and characterized using ultraviolet-visible (UV-Vis) spectrophotometer, dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. Te antimicrobial activity of the GA-AgNPs was evaluated on Streptococcus sanguinis (S. sanguinis), Streptococcus mutans (S. mutans), Lactobacillus acidophilus (L. acidophilus), and Candida albicans (C. albicans) using agar disc diffusion and microdilution assays

Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings

Computational insight of dexamethasone against potential targets of SARS-CoV-2

The health sector has been on the race to find a potent therapy for coronavirus disease (COVID)-19, a diseases caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Repurposed anti-viral drugs have played a huge role in combating the virus, and most recently, dexamethasone (Dex) have shown its therapeutic activity in severe cases of COVID-19 patients. The study sought to provide insights on the anti-COVID-19 mechanism of Dex at both atomic and molecular level against SARSCoV-2 targets. Computational methods were employed to predict the binding affinity of Dex to SARSCoV-2 using the Schrodinger suite (v2020-2). The target molecules and ligand (Dex) were retrieved from PDB and PubChem, respectively. The selected targets were SARS-CoV-2 main protease (Mpro), and host secreted molecules glucocorticoid receptor, and Interleukin-6 (IL-6). Critical analyses such as Protein and ligand preparation, molecular docking, molecular dynamic (MD) simulations, and absorption, distribution, metabolism, excretion (ADME), and toxicity analyses were performed using the targets and the ligand as inputs