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1.
ADMET DMPK ; 12(2): 379-389, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720924

RESUMO

Background and purpose: Lymphatic filariasis is a debilitating infectious disease prevalent in endemic areas, necessitating the development of an effective vaccine for eradication. Although recombinant vaccine candidates have been deemed safe, they often fail to provide sufficient protection, which can be overcome by encapsulating them in nano-liposomes. In this study, we have optimised the liposomal composition for enhanced stability and encapsulation of filarial antigen Brugia malayi thioredoxin (Bm-TRX). Experimental approach: Nano-liposomes were prepared using egg phosphatidylcholine (EPC) and cholesterol via thin-film hydration, followed by sonication and characterizing. Encapsulation efficiency was optimised using different weight ratios of EPC to cholesterol (8:2, 7:3, and 6:4) and total lipid (EPC+Cholesterol) concentration to antigen Bm-TRX (10:1, 10:2, and 10:3) followed by release kinetics study. Key results: Optimised parameters yielded spherical liposomes measuring 209 nm in diameter with narrow polydispersity. Our findings demonstrated the highest encapsulation efficiency of 70.685 % and stability of 10 hours for an EPC to cholesterol weight ratio of 7:3. The in silico study proved the antigenic nature of TRX. Conclusion: The liposomal formulations loaded with TRX, as optimized in this study, hold promise for improving antigen efficiency by enhancing stability, bioavailability, and prophylactic effects by acting as immune potentiators.

2.
Int J Biol Macromol ; 222(Pt B): 2392-2398, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220408

RESUMO

Lymphatic filariasis is a parasitic disease caused by nematodes affecting millions of individuals in the tropical region. The complex life cycle of the filarial parasite eludes protective measures such as chemotherapy and vector control. Vaccination through recombinant proteins stands as one of the safe and most effective methods. The filarial antigens Brugia malayi Thioredoxin (TRX) and abundant larval transcript-2 (ALT-2) can induce recognizable levels of protection in murine animal models. Chitosan is a safe, non-toxic material ubiquitously served as an efficient carrier and an adjuvant. The present study was attempted to enhance the immune efficacy of filarial antigens using chitosan nanoparticles (CN) through mucosal routes of immunization. Our study showed that oral immunization was able to produce enhanced humoral response and balanced Th1/Th2 antibody isotype response for the recombinant antigens compared to intranasal routes. A high level of splenocyte T cell proliferation (P < 0.01) was obtained for both routes. The cytokine analysis showed a high level of IFN-γ followed by IL-5 for the oral route, whereas a high level of IL-4 was observed for intranasal route. These results confirm the ability of chitosan nanoparticles to elevate the immune efficacy of the antigens through the oral route in mice.


Assuntos
Brugia Malayi , Quitosana , Filariose Linfática , Nanopartículas , Vacinas , Camundongos , Animais , Filariose Linfática/prevenção & controle , Filariose Linfática/parasitologia , Camundongos Endogâmicos BALB C , Imunização , Vacinação
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