Ivermectin-loaded microparticles for parenteral sustained release:in vitrocharacterization and effect of some formulation variables

Abstract

Ivermectin (IVM) is a BCS II drug with potent antiparasitic activity in veterinary applications. In this study, poly(lactide-co-glycolide) (PLGA) and poly(DL-lactide) (PLA) Ivermectin-loaded microparticles were prepared by the simple emulsion (O/W) solvent evaporation method in order to obtain sustained release formulations for parenteral applications. The effects of polymer end-groups (ester or free acid) and the addition of the hydrophilic polyvinylpyrrolidone polymer (PVP) in in vitro drug release profiles were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that IVM was present in an amorphous state or as a molecular dispersion within the polymers or theirs mixtures with PVP and that a PVP-drug complex was formed. Drug entrapment efficiency in the microparticles (>90%) was independent of the polymer composition, the end groups and the presence of PVP. However, microscopic (SEM) observations showed that the addition of PVP led to more porous microparticles accompanied by the increased rates of drug release.

Influence of charge on FITC-BSA-loaded chondroitin sulfate-chitosan nanoparticles upon cell uptake in human Caco-2 cell monolayers

“…3,4 Nanoparticles with a suitable nanosize may potentially penetrate into tissues by passing through fenestrations present in the epithelial lining of blood vessels and being taken up by cells in these tissues. [5][6][7] This pathway involves the enhanced permeability and retention effect which allows the efficient delivery of therapeutic agents to specific target sites in the body.…”

Δ2,3 -Ivermectin ethyl secoester, a conjugated ivermectin derivative with leishmanicidal activity but without inhibitory effect on mammalian P-type ATPases

“…As we do not know the fine mechanism of ivermectin inhibition of this enzyme, albeit we reported some details in a previous work (Pimenta et al 2010), it could be argued that ivermectin should penetrate the membrane to interact with some putative intracellular locus of the transmembrane ATPases (Na + ,K + -ATPase and H + ,K + -ATPase). Note that ivermectin is very lipophilic (Log P of 3.217, 4.8, and 5.31 have been reported by Camargo et al 2010;Kiki-Mvouaka et al 2010 andBaynes 2009, respectively), so that it can easily penetrate the plasma membrane and reach the internal loops of these enzymes. It could also penetrate the cell and reach the SERCA, as occurs with thapsigargin, a lipophylic sequiterpene lactone that specifically inhibits this Ca 2+ -ATPase located in the sarco-endoplasmic reticulum.…”

Ivermectin: an award-winning drug with expected antiviral activity against COVID-19

“…Micro-and nanocarriers offer several advantages in drug delivery, namely: specific targeting, high metabolic stability, high membrane permeability, improved bioavailability, controlled release and long-lasting action [ 30 ]. In light of these attributes, some studies have formulated ivermectin in micro- and nanoparticles, either using lipid nanocapsules [ 31 ], chitosan-alginate nanoparticles [ 32 ] or poly (lactic- co -glycolic acid) (PLGA) micro- and nanoparticles [ 33 , 34 ]. For antiviral purposes, ivermectin has been formulated in liposomes [ 35 ] and PLGA nanoparticles [ 29 ].…”