Pyromellitic dianhydride crosslinked soluble cyclodextrin polymers: Synthesis, lopinavir release from sub-micron sized particles and anti-HIV-1 activity

Adeoye, Oluwatomide; Bártolo, Inês; Conceição, Jaime; Bento-Silva, Andreia; Duarte, Noélia; Francisco, Ana Paula; Taveira, Nuno; Marques, Helena Cabral

http://hdl.handle.net/10451/58961

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Autores

Marques, Helena Cabral

Resumo(s)

We report the synthesis of water soluble cyclodextrin (CD) polymers prepared by crosslinking pyromellitic dianhydride (PMDA) with two CD derivatives (methyl-β-CD - MβCD and (2-hydroxy)propyl-β-CD - HPβCD) and their evaluation as functional sub-micron sized carriers in the development of antiretroviral drug delivery systems. Using the protease inhibitor lopinavir (LPV) as model drug, LPV loaded CD polymers (pHPβCD and pMβCD) were prepared and fully characterized. The physicochemical characterization and in vitro drug release confirmed the successful synthesis of pHPβCD and pMβCD, the formation of sub-micron sized particles and a 12–14 fold increase in LPV solubility. Cytotoxicity assays indicated that both pHPβCD and pMβCD were able to improve the safety profile of LPV while the viral infectivity assay revealed a concentration independent anti-HIV-1 effect for both pHPβCD and pMβCD with a maximum percentage inhibition (MPI) of 79 and 91% respectively. After LPV loading, the antiviral profile of pHPβCD was reversed to the sigmoidal dose–response profile of LPV, while pMβCD maintained its dose-independent profile followed by a LPV mediated increase in viral inhibition. Overall, both pHPβCD and pMβCD demonstrated anti-HIV-1 activity, while drug loaded pMβCD indicated its potential as functional sub-micron sized drug delivery polymers for achieving synergistic anti-HIV activity.

Palavras-chave

Cyclodextrin nanosponges Aluviran (2-Hydroxy)propyl-β-cyclodextrin Methyl-β-cyclodextrin HIV/AIDS Antiviral activity

URI

http://hdl.handle.net/10451/58961

Citação

Adeoye O, Bártolo I, Conceição J, da Silva AB, Duarte N, Francisco AP, et al. Pyromellitic dianhydride crosslinked soluble cyclodextrin polymers: Synthesis, lopinavir release from sub-micron sized particles and anti-HIV-1 activity. International Journal of Pharmaceutics [Internet]. 15 de junho de 2020;583:119356. Disponível em: https://www.sciencedirect.com/science/article/pii/S0378517320303409