Browsing by Author "Ahmed, Rami"

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    Synthesis of immunomodulatory biomimetic lipid polymer hybrid nanoparticles and application of zebrafish larvae in immunomodulation screening
    (Elsevier B.V., 2025) Irabin, Aime; Ahmed, Rami; Dube, Admire
    Since the antibiotic golden era of the mid-20th century, there have been limited antibiotics approved, while antibiotic resistance continues to escalate disproportionately, outpacing the rate of novel antibiotic discovery. This imbalance poses a serious global health concern, with an estimated annual death toll of 10 million due to antibiotic resistance by 2050. There is a growing interest in immunotherapy as an alternative approach to conventional antibiotics due to its ability to target and stimulate immune system, leveraging its innate ability to self-eradicate pathogens. This study synthesized lipid polymer hybrid nanoparticles (LPHNPs) conjugated with two immunomodulatory agents, namely, curdlan and mycolic acid (MA), as a potential immunotherapy for bacterial infections. LPHNPs were synthesized using lecithin and polycaprolactone (PCL) at a 15 % lipid-to-polymer (w/w) ratio. Additionally, PCL-curdlan copolymer, comprising 15 % w/w curdlan, was successfully synthesized and used to conjugate the LPHNPs with various curdlan concentrations. Furthermore, The LPHNPs were conjugated with varying MA concentrations, with or without curdlan. In-vivo assessment of the immunomodulatory effect of the LPHNPs was conducted using a larval zebrafish model assessing behaviour and immunofluorescence, as indicators of immune stimulation. The data suggests that curdlan exhibits a more complex immunoregulatory role as demonstrated by the countered stimulated behavioural effect while inflammation remained heightened. This work also provides new insights that zebrafish larvae are a valuable screening tool in the development of nanoparticle immunotherapies.
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    Vitamin D3 loaded polycaprolactone nanoparticles enhance the expression of the antimicrobial peptide cathelicidin in macrophages
    (Taylor and Francis Ltd., 2025) Dlozi, Prince; Ahmed, Rami; Khoza, Star; Dube, Admire
    Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis, remains a global health burden. Current antibiotic treatments are limited by adverse effects, poor adherence, and drug resistance, necessitating new therapeutic approaches. Recent studies highlight the role of vitamin D3 (VD3) in enhancing host immune responses against the mycobacterium via cathelicidin (an antimicrobial peptide) and autophagy activation. In this study, VD3-loaded poly-ƹ-caprolactone (PCL) nanoparticles (NPs) were synthesized to enhance cathelicidin expression in macrophages. NPs containing cholecalciferol, calcifediol, and calcitriol were synthesized using an emulsification solvent-evaporation technique. Average sizes of synthesized NPs ranged from 304.7 to 458.7 nm, with polydispersity index (PDI) and zeta potential (ZP) ranging from 0.103 to 0.257 and −17.3 to −7.47 mV, respectively. Encapsulation efficiencies were 9.68%, 10.99%, and 19.28% for cholecalciferol, calcifediol, and calcitriol, respectively. VD3-encapsulated NPs stimulated a dose-dependent increase in cathelicidin expression in THP-1 macrophages. Encapsulated calcifediol and calcitriol (100 ng/ml) induced the expression of 243.46 ng/ml ± 4.55 ng/ml and 396.67 ng/ml ± 25.24 ng/ml of cathelicidin, respectively, which was significantly higher than that induced by the free drugs. These findings suggest that NP encapsulation may offer a more efficient approach to using vitamin D3 for inducing cathelicidin expression as a host-directed treatment for TB.