In last years, curcumin (diferuloymethane; CUR) has demonstrated various effects on crucial molecular targets, related to many pathologies including cancer, inflammation, arthritis, diabetes, Crohn’s disease. CUR is however characterized by a very poor aqueous solubility and limited oral adsorption (BCS class IV compound). To ameliorate the photostability and oral bioavailability of CUR, the drug has been microencapsulated in polymethacrylate polymers (Eudragit® Retard). A solution of CUR in acetone mas mixed at various drug-to-polymer (DPR) ratios with ethanol solution of Eudragit® RL100/RS100 blends, at different weight composition, and the mixture was added dropwise, under stirring at r.t., to an aqueous phase containing 0.02 % (w/v) Tween 80. After solvent evaporation at r.t., the suspension was lyophilized and sieved to collect the 420-90 m microparticle fractions. The systems were characterized in the solid state for micromeritic properties and drug loading, and by FT-IR, PXRD and DSC for their physico-chemical state. Encapsulation efficiency largely varied from 35 to 95%, mainly depending on the copolymer composition and to a less extent from DPR. Solid-state characterization confirmed the chemical stability of CUR in microparticles, also after 6 months of storage at 25 or 40 °C, and suggested that the drug was in a microcrystalline form within the polymer matrix, as also shown by light microscopy analysis. Interestingly, the polymeric matrix showed to protect CUR from UV-induced photodegradation, with an effect related to the drug-to-polymer ratio (DPR). Although a limited effect was exerted by microencapsulation on the solubility and dissolution profile of CUR in gastro-intestinal environments, in vitro and in vivo assays respectively showed an enhanced permeation of microencapsulated CUR through Caco-2 monolayers, compared to the neat drug, and a 7-fold increase of oral bioavailability. These data can be related to the bio- and mucoadhesivity shown by Eudragit® microparticles in vitro, using respectively Caco-2 cell monolayers and HT29MTXE12 (E12) intestinal cells monolayers, a goblet cell-like subclone of the human colon carcinoma HT29 cell line, which is able to secrete an adherent mucus layer. Furthermore, an ex vivo inverted rat intestine model confirmed the mucoadhesive properties of these microparticles: application of CUR-loaded microparticles with a DPR value of 1:5 and 1:10 led to 50% and 40% residual CUR on the intestine surface, respectively, compared to the neat drug that was completely removed after washing out.

MICROENCAPSULATION WITH METHACRYLIC COPOLYMERS IMPROVES THE ORAL BIOAVAILABILITY OF CURCUMIN

PIGNATELLO, Rosario;
2016

Abstract

In last years, curcumin (diferuloymethane; CUR) has demonstrated various effects on crucial molecular targets, related to many pathologies including cancer, inflammation, arthritis, diabetes, Crohn’s disease. CUR is however characterized by a very poor aqueous solubility and limited oral adsorption (BCS class IV compound). To ameliorate the photostability and oral bioavailability of CUR, the drug has been microencapsulated in polymethacrylate polymers (Eudragit® Retard). A solution of CUR in acetone mas mixed at various drug-to-polymer (DPR) ratios with ethanol solution of Eudragit® RL100/RS100 blends, at different weight composition, and the mixture was added dropwise, under stirring at r.t., to an aqueous phase containing 0.02 % (w/v) Tween 80. After solvent evaporation at r.t., the suspension was lyophilized and sieved to collect the 420-90 m microparticle fractions. The systems were characterized in the solid state for micromeritic properties and drug loading, and by FT-IR, PXRD and DSC for their physico-chemical state. Encapsulation efficiency largely varied from 35 to 95%, mainly depending on the copolymer composition and to a less extent from DPR. Solid-state characterization confirmed the chemical stability of CUR in microparticles, also after 6 months of storage at 25 or 40 °C, and suggested that the drug was in a microcrystalline form within the polymer matrix, as also shown by light microscopy analysis. Interestingly, the polymeric matrix showed to protect CUR from UV-induced photodegradation, with an effect related to the drug-to-polymer ratio (DPR). Although a limited effect was exerted by microencapsulation on the solubility and dissolution profile of CUR in gastro-intestinal environments, in vitro and in vivo assays respectively showed an enhanced permeation of microencapsulated CUR through Caco-2 monolayers, compared to the neat drug, and a 7-fold increase of oral bioavailability. These data can be related to the bio- and mucoadhesivity shown by Eudragit® microparticles in vitro, using respectively Caco-2 cell monolayers and HT29MTXE12 (E12) intestinal cells monolayers, a goblet cell-like subclone of the human colon carcinoma HT29 cell line, which is able to secrete an adherent mucus layer. Furthermore, an ex vivo inverted rat intestine model confirmed the mucoadhesive properties of these microparticles: application of CUR-loaded microparticles with a DPR value of 1:5 and 1:10 led to 50% and 40% residual CUR on the intestine surface, respectively, compared to the neat drug that was completely removed after washing out.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/111101
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