RESUMO
The purpose of the study was to (i) prepare the chitosan/Kollicoat SR 30D film-coated pellets for colonic drug delivery, and (ii) evaluate the colonic delivery and efficacy of these coated pellets in the rat. The pellets were coated to different film thickness with chitosan/Kollicoat SR 30D formulations. In vitro drug release was assessed in simulated gastrointestinal (GI) tract conditions. Biodistribution of aminosalicylates (5-ASA) in GI tract and plasma was measured after oral administration of coated or uncoated 5-ASA pellets. Efficacy of the coated or uncoated 5-ASA pellets was tested in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model. Healing of induced colitis was assessed by measuring the myeloperoxidase activities, colon wet weight/body weight, and damage score. The coating was susceptible to bacteria digestion, resulting in an increase in the release of 5-ASA from the coated pellets. After administration of the coated pellets, the drug concentration in the large intestine was higher than those of uncoated pellets. In plasma, the observed mean C(max) from the coated pellets was significantly lower than that of the uncoated pellets. Chitosan/Kollicoat SR 30D film-coated pellets could deliver the 5-ASA to the targeted site, providing effective treatment for inflammatory bowel disease.
Assuntos
Ácidos Aminossalicílicos/administração & dosagem , Quitosana/química , Colo/metabolismo , Portadores de Fármacos/química , Polivinil/química , Ácidos Aminossalicílicos/química , Ácidos Aminossalicílicos/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Microscopia Eletrônica de Varredura , Ratos , Solubilidade , Propriedades de Superfície , Comprimidos com Revestimento Entérico , Distribuição TecidualRESUMO
OBJECTIVES: The purpose of the study was to evaluate digestion of pectin/Kollicoat SR30D free films for colonic delivery in vitro and in vivo. METHODS: Free films containing different ratios of pectin to Kollicoat SR30D were prepared by casting/solvent evaporation method. An in-vitro comparison of swelling, degradation and permeability of the free films was carried out in simulated colon fluids containing caecal contents from normal rats with colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) or oxazolone. A comparative in-vivo evaluation of degradation was also conducted in normal and colitis-induced model rats. KEY FINDINGS: The pectin within the mixed films was susceptible to rat colonic bacterial enzymes. The extent of digestion correlated with the amount of pectin present within the film. In vitro, the swelling index, drug permeability and extent of film digestion in simulated colon fluids with caecal contents obtained from normal rats were higher than from TNBS- or oxazolone-induced model rats, whereas in-vivo degradation was similar in the three groups of rats. The pectin/Kollicoat SR30D free films were completely degraded in the colitis-induced rats. CONCLUSIONS: Pectic/Kollicoat SR30D films may be useful as coatings to target delivery of drugs to the colon.
Assuntos
Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/microbiologia , Sistemas de Liberação de Medicamentos/métodos , Pectinas/química , Polivinil/química , Animais , Ceco/efeitos dos fármacos , Ceco/microbiologia , Ceco/fisiopatologia , Colite/induzido quimicamente , Colo/enzimologia , Modelos Animais de Doenças , Fluoruracila/normas , Fluoruracila/toxicidade , Vidro/química , Oxazolona/toxicidade , Pectinas/farmacologia , Permeabilidade , Polivinil/farmacologia , Ratos , Vapor , Temperatura , Ácido Trinitrobenzenossulfônico/toxicidadeRESUMO
The purpose of the study was to establish the physico-mechanical, digestibility, permeability and swelling properties of chitosan/Kollicoat SR30D films as potential coatings for colonic drug delivery. Free films containing different ratios of chitosan to Kollicoat SR30D were prepared by casting/solvent evaporation method. The resultant mixed films were characterized in terms of puncture strength and elongation (%), glass transition temperature, swellability, polymer miscibility, permeability, and digestibility under different media. The mixed films possessed good mechanical properties, which could be used as film-coating materials for drug delivery. The extent of digestion was directly proportional to the amount of chitosan present within the film. No apparent miscibility was detected between the chitosan and Kollicoat SR30D, regardless of the film composition. The films were found to be susceptible to digestion by bacterial or beta-glucosidase enzymes in simulated colonic fluid (SCF). The SCF with rat cecal bacterial enzymes had a more profound hydrolytic activity than that with beta-glucosidase enzyme for the digestion of chitosan within the mixed films. Overall, the results indicated that such chitosan/Kollicoat SR30D films had potential as a coating system for drug delivery to the colon.
