Design of Mannose-Coated Rifampicin nanoparticles modulating the immune response and Rifampicin induced hepatotoxicity with improved oral drug delivery
| Autor: | Mansoor Abdullah Sandhu, Aisha Rauf, Sadanand Pandey, Sabira Tahseen, Gul Shahnaz, Tanveer A. Tabish, Magali Cucchiarini, Muhammad Rauf ul Hassan, Abbas Rahdar, Ibrahim M. Ibrahim |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Hepatoptotective
Chemistry General Chemical Engineering technology industry and agriculture General Chemistry Glutathione Pharmacology medicine.disease Chitosan nanoparticles Hemolysis Bioavailability Biomaterials Immunomodulation chemistry.chemical_compound Pharmacokinetics Oral administration In vivo Toxicity Drug delivery medicine Mucoadhesion QD1-999 Rifampicin |
| Zdroj: | Arabian Journal of Chemistry, Vol 14, Iss 9, Pp 103321-(2021) |
| ISSN: | 1878-5352 |
| Popis: | We have demonstrated the enhanced in vivo oral efficacy and enhanced hepatoprotective effects of preactivated thiolated chitosan (Cht) nanoparticles (NPs) for tuberculosis. The mannose anchored preactivated thiolated chitosan nanoparticles (MPTCht-NPs) were prepared and characterized in terms of their particle size, in vitro entrapment efficiency (EE%) and zeta potential (mV). NPs were also evaluated in terms of mucoadhesion, % hemolysis, permeation enhancement, in vivo pharmacokinetics, toxicity and immunomodulation. NPs exhibited an average particle size of 307 nm with 19 folds enhanced permeation in comparison to conventional Rifampicin (Rif) formulation across everted rat intestine. The evaluation of in vivo pharmacokinetic parameters indicated 16 folds improvement in oral bioavailability in comparison to Rif alone following oral administration in rabbits. There was significant difference in the levels of serum transaminases, oxidative stress markers, and expression levels of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) genes between Rif treated and NPs treated groups. The serum transaminases levels were normal with MPTCht-NPs treated groups as compared to Rif treated groups while the levels of glutathione were markedly increased in MPTCht-NPs treated group. Furthermore, the levels of Bax were enhanced with the MPTCht-NPs treatment. In summary, these findings revealed that the designed NPs may act as promising therapeutic strategy against tuberculosis in a dose-dependent manner while providing the immunomodulation and hepatoprotective effect. |
| Databáze: | OpenAIRE |
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