Colon-specific Delivery of Budesonide with Azopolymer-coated Pellets: Therapeutic Effects of Budesonide with a Novel Dosage Form against 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Tozaki, Hideyuki; Fujita, Takuya; Komoike, Junta; Kim, Sooh‐Ih; Terashima, Hiroshi; Muranishi, Shozo; Okabe, Susumu; Yamamoto, Akira

doi:10.1211/0022357991772420

Cited by 32 publications

(12 citation statements)

References 12 publications

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“…Colonic in¯ammatory lesions were induced by the method of Morris et al (1989) and Tozaki et al (1999). TNBS (20 mg in 0Á25 mL 50% ethanol) was instilled into the colon via the anus of the rats.…”

Section: Induction Of Colonic In¯ammation and Treatment Of Ulcerativementioning

confidence: 99%

Validation of a Pharmacokinetic Model of Colon-specific Drug Delivery and the Therapeutic Effects of Chitosan Capsules Containing 5-Aminosalicylic Acid on 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Tozaki

Fujita

Odoriba

et al. 1999

Journal of Pharmacy and Pharmacology

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A pharmacokinetic model of colon-specific drug delivery developed in a previous study has been validated by use of 5-aminosalicylic acid (5-ASA) as a model anti-inflammatory drug. The simulation curves obtained from the pharmacokinetic model were in good agreement with experimental data obtained after oral administration of 5-ASA-containing chitosan capsules. The concentrations of 5-ASA in the large intestinal mucosa after drug administration were higher than after administration of the drug in carmellose suspension. We then attempted colon-specific delivery of an anti-ulcerative colitis drug, in chitosan capsules, to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. To confirm this therapeutic model, salazosulphapyridine (SASP), a commercially available 5-ASA prodrug, was used as positive control. Colonic injury and inflammation were assessed by measuring myeloperoxidase activity and visual assessment (damage score), respectively. Because SASP is effective against TNBS-induced colitis in rats, use of the SASP-sensitive TNBS-induced colitis model validated the therapeutic effects of 5-ASA-containing chitosan capsules, which were significantly better than those of a suspension of the drug in carmellose. These findings suggest that our pharmacokinetic model of colon-specific drug delivery can accurately evaluate this colon-specific delivery system and that 5-ASA-containing chitosan capsules are more effective than other 5-ASA formulations for treatment of TNBS-induced colitis in rats.

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Section: Induction Of Colonic In¯ammation and Treatment Of Ulcerativementioning

confidence: 99%

Validation of a Pharmacokinetic Model of Colon-specific Drug Delivery and the Therapeutic Effects of Chitosan Capsules Containing 5-Aminosalicylic Acid on 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Tozaki

Fujita

Odoriba

et al. 1999

Journal of Pharmacy and Pharmacology

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“…For this purpose, male Wistar rats were treated with an enema containing trinitrobenzene sulfonic acid (TNBS) in ethanol-water 1:1 v/v mixture (see Experimental section for details). The main advantages of this model are its simplicity, reproducibility and time and dose related development of inflammation [53,54]. The development of the inflammation was monitored daily.…”

mentioning

confidence: 99%

Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment

Teruel

Pérez‐Esteve

González‐Álvarez

et al. 2018

Journal of Controlled Release

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Magnetic mesoporous silica microparticles were loaded with safranin O (S1) and with hydrocortisone (S2) and the outer surface functionalized with a bulky azo derivative bearing urea moieties. Aqueous suspensions of both solids at pH 7.4 showed negligible payload release whereas a marked delivery was observed in the presence of sodium dithionite due to the rupture of the azo bonds. Besides, a moderate cargo release was observed at acidic pH due to the hydrolysis of the urea bonds that linked the azo derivative onto the external surface of the inorganic scaffolds. In vitro digestion models showed that S1 and S2 microparticles could be used for the controlled release of payload in the reducing colon environment (in which azoreductase enzymes are present). On the other hand, in vivo pharmacokinetic studies in rats showed that safranine O release from S1 microparticles was concentrated in colon. The performance of S2 microparticles for the treatment of colitis in rats (induced by oral administration of a 2,4,6-trinitrobenzenesulfonic acid solution) was tested. The controlled release of hydrocortisone from S2 in the colon of injured rats induced marked reduction in colon/body weight ratio and in clinical activity score. Also, histological studies showed a marked decrease in inflammation followed by intensive regeneration and almost normal mucosal structure of the individuals treated with S2. Besides, the use of a magnetic belt increased the therapeutic performances of S2 due to an enhanced retention time of the particles in the colon.

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“…This colonic delivery system, the site-specificity of which is based on combining pH-sensitive and controlled drug delivery properties, caused a significant decrease in inflammation in the colon of colitic rats after oral administration, compared with the same dose of drug administered as an oral suspension. Similar studies carried out with novel colonic delivery systems containing BDS, such as glucuronide prodrugs (Cui et al 1994) or azopolymer-coated pellets (Tozaki et al 1999a), revealed the increased efficacy of the systems compared with oral administration of the free drug. However, results from those works indicated that not all the parameters measured (i.e.…”

Section: Discussionmentioning

confidence: 56%

Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats

Rodríguez

Antúnez

Taboada

et al. 2001

Journal of Pharmacy and Pharmacology

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Budesonide (BDS) is a potent corticosteroid that has important implications in the pharmacotherapy of inflammatory bowel disease, especially in the treatment of ulcerative colitis and Crohn's disease. BDS is available on the market in the form of enteric-coated preparations. However these products, similar to other available site-specific dosage forms, are not sufficiently selective to treat colonic inflammatory bowel disease. The objective of this study was to evaluate the efficacy of a new microparticulate system containing BDS, to treat experimentally induced colitis in rats. This microparticulate system consisted of BDS-containing hydrophobic cores, microencapsulated within an enteric polymer, which solubilizes at above pH 7, thus combining pH-sensitive and controlled-release properties. Colonic injury and inflammation were assessed by measuring colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring macroscopic and histological damage in colitic rats. Rats were treated orally with BDS, included in the developed system, once a day for 4 days after the induction of inflammation. A BDS suspension and BDS-containing enteric microparticles were included as control formulations in the experimental design. The administration of the new BDS delivery system significantly reduced the colon/bodyweight ratio compared with the administration of control formulations. Similarly, MPO activity and macroscopic and histological damage of the inflamed colonic segments decreased significantly when the BDS formulation was administered, compared with the results obtained after oral administration of the drug suspension. There were no significant differences, however, when the new treatment was compared with the control formulation consisting of simple enteric microparticles.

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Colon-specific Delivery of Budesonide with Azopolymer-coated Pellets: Therapeutic Effects of Budesonide with a Novel Dosage Form against 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Cited by 32 publications

References 12 publications

Validation of a Pharmacokinetic Model of Colon-specific Drug Delivery and the Therapeutic Effects of Chitosan Capsules Containing 5-Aminosalicylic Acid on 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Validation of a Pharmacokinetic Model of Colon-specific Drug Delivery and the Therapeutic Effects of Chitosan Capsules Containing 5-Aminosalicylic Acid on 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment

Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats

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