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Liposomal delivery system/adjuvant for tuberculosis vaccine.

ABSTRACT: As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next-generation TB vaccines.

SUBMITTER: Moradi M

PROVIDER: S-EPMC10251763 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Liposomal delivery system/adjuvant for tuberculosis vaccine.

Moradi Melika M Vahedi Farzaneh F Abbassioun Arian A Ramezanpour Shahi Arash A Sholeh Mohammad M Taheri-Anganeh Mortaza M Dargahi Zahra Z Ghanavati Roya R Khatami Seyyed Hossein SH Movahedpour Ahmad A

Immunity, inflammation and disease 20230601 6

As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, partic ...[more]

PMID: 37382263

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Project description:Glycosylated NPs, including liposomes, are known to target various receptors involved in cellular carbohydrate transport, of which the mannoside binding receptors are attracting particular attention for their expression on various immune cells, cancers, and cells involved in maintaining central nervous system (CNS) integrity. As part of our interest in NP drug delivery, mannosylated glycoliposomal delivery systems formed from the self-assembly of amphiphilic neoglycolipids were developed, with a C12-alkyl mannopyranoside (ML-C12) being identified as a lead compoundcapable of entrapping, protecting, and improving the delivery of structurally diverse payloads. However, ML-C12 was not without limitations in both the synthesis of the glycolipids, and the physicochemical properties of the resulting glycoliposomes. Herein, the chemical syntheses of a novel series of mannosylated neoglycolipids are reported with the goal of further improving on the previous ML-C12 glyconanoparticles. The current work aimed to use a self-contingent strategy which overcomes previous synthetic limitations to produce neoglycolipids that have one exposed mannose residue, an aromatic scaffold, and two lipid tails with varied alkyl chains. The azido-ending carbohydrates and the carboxylic acid-ending lipid tails were ligated using a new one-pot modified Staudinger chemistry that differed advantageously to previous syntheses. The formation of stable neoglycoliposomes of controllable and ideal sizes (≈100-400 nm) was confirmed via dynamic light scattering (DLS) experiments and transmission electron microscopy (TEM). Beyond chemical advantages, the present study further aimed to establish potential improvements in the biological activity of the neoglycoliposomes. Concanavalin A (Con A) agglutination studies demonstrated efficient and stable cross-linking abilities dependent on the length of the linkers and lipid tails. The efficacy of the glycoliposomes in improving cytosolic uptake was investigated using Nile Red as probe in immune and cancer cell lines. Preliminary ex vivo safety assessments showed that the mannosylated glycoliposomes are hemocompatible, and non-immunogenic. Finally, using a model peptide therapeutic, the relative entrapment capacity and plasma stability of the optimal glycoliposome delivery system was evaluated and compared to the previous neoglycoliposomes. Overall, the new lead glycoliposome showed improved biological activity over ML-C12, in addition to having several chemical benefits including the lack of stereocenters, a longer linker allowing better sugar availability, and ease of synthesis using novel one-pot modified Staudinger chemistry.

Dataset Information

Liposomal delivery system/adjuvant for tuberculosis vaccine.

Publications

Liposomal delivery system/adjuvant for tuberculosis vaccine.

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