Showing papers by "Benoit Barbeau published in 2023"

Anionic and Ampholytic High-Amylose Starch Derivatives as Excipients for Pharmaceutical and Biopharmaceutical Applications: Structure-Properties Correlations

Abstract: Many chemical modifications of starch are realized in organic (mostly methanol) phase, allowing high degrees of substitution (DS). Some of these materials are used as disintegrants. To expand the usage of starch derivative biopolymers as drug delivery system, various starch derivatives obtained in aqueous phase were evaluated with the aim to identify materials and procedures which would generate multifunctional excipients providing gastro-protection for controlled drug delivery. Chemical, structural and thermal characteristics of anionic and ampholytic High Amylose Starch (HAS) derivatives under powder (P), tablet (T) and film (F) forms were evaluated by X-ray Diffraction (XRD), Fourier Transformed Infrared (FTIR) and thermogravimetric analysis (TGA) methods and correlated with the behavior of tablets and films in simulated gastric and intestinal media. At low DS, the HAS carboxymethylation (CMHAS) in aqueous phase, generated tablets and films that were insoluble at ambient conditions. The CMHAS filmogenic solutions, with a lower viscosity, were easier to cast and gave smooth films without the use of plasticizer. Correlations were found between structural parameters and the properties of starch excipients. Compared to other starch modification procedures, the aqueous modification of HAS generated tunable multifunctional excipients that may be recommended for tablets and functional coatings for colon-targeted formulations.

Infection of the Ex Vivo Tonsil Model by HTLV-1 Envelope-Pseudotyped Viruses

Abstract: Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. Its tropism is known to be broad in cultured cell lines, while in vivo data support a more selective transmission toward CD4+ T cells and the limited targeting of other hematopoietic cell types. An essential condition for HTLV-1 infection is cell-to-cell contact, to which both virological synapse and viral biofilm have been suggested to strongly contribute. As cell lines and animal models each present their own limitations in studying HTLV-1 replication, we have explored the use of an ex vivo model based on the secondary lymphoid tonsillar tissue. HIV-1 luciferase-expressing pseudotyped viruses bearing the HTLV-1 envelope protein at their surface were first shown to recapitulate the wide spectrum of infectivity of HTLV-1 toward various cell lines. Tonsil fragments were next exposed to pseudotyped viruses and shown to be reproducibly infected. Infection by HTLV-1 Env-pseudotyped viruses was blocked by different anti-gp46 antibodies, unlike infection by HIV-1 virions. The dose-dependent infection revealed a gradual increase in luciferase activity, which was again sensitive to anti-gp46 antibodies. Overall, these results suggest that the ex vivo tonsil model represents a reliable alternative for studying HTLV-1 replication and potentially viral latency, as well as early clonal formation.