Kinetics of hydrolysis of dextran–methylprednisolone succinate, a macromolecular prodrug of methylprednisolone, in rat blood and liver lysosomes

Mehvar, Reza; Dann, Roger O; Hoganson, Dean A

doi:10.1016/s0168-3659(00)00234-0

Cited by 39 publications

(26 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Low molecular weight Dex are eliminated from the circulation via kidney ultrafiltration, while larger polymers dispose predominantly in the liver, spleen, and lymph nodes where they can be degraded by dextranases and other esterares [96]. Comparative studies performed by using Dex derivatives with different molecular weights and charge pointed out the effects of these structural features on their pharmacokinetic behavior [97][98][99]. The permanence of dextrans in the bloodstream increased as the size increased, according to the reduced ultrafiltration [100].…”

Section: Dextranmentioning

confidence: 99%

“…It was in fact found that colloidal formulations of MP can target the drug to the spleen to be more effective than the free drug in an experimental model of heart transplantation. Since Dex was demonstrated to deliver conjugated drugs to reticuloendothelial tissues such as the liver and spleen which are major organs responsible for the immune response, the MP conjugation to Dex was considered a valuable tool to improve the immunosuppressive performance of this drug [131,132].…”

Section: Methylprednisolone and Tacrolimusmentioning

confidence: 99%

“…MP and Succ-MP were released in the lysosomal fraction about 50-fold more slowly than in blood, suggesting that the levels of esterases in the lysosomal fraction are lower than in blood. In lysosomes the drug release occurred mainly through chemical cleavage [132].…”

Section: Methylprednisolone and Tacrolimusmentioning

confidence: 99%

See 2 more Smart Citations

Polysaccharide-Based Anticancer Prodrugs

Caliceti

Salmaso

Bersani

2009

Macromolecular Anticancer Therapeutics

View full text Add to dashboard Cite

So far, polysaccharides have been widely used in pharmaceutical technology as first choice excipients for production of traditional formulations. Nevertheless, in the recent years these natural and semisynthetic macromolecules have been addressed for new challenging applications as functional materials for innovative formulations. Their peculiar physicochemical and biological properties have been exploited to develop macromolecular prodrugs which can exhibit favorable biopharmaceutical properties and enforce the therapeutic performance of the parent drugs. These polymers display, in fact, high biocompatibility and biodegradability, multiple insertion points, and biological properties that can be advantageously exploited in drug delivery. In particular, the multifunctional structures of these polymers are anchoring points for conjugation of several anticancer drugs, which usually suffer from poor physicochemical, biopharmaceutical, and therapeutic properties that limit their therapeutic performance and proper use in anticancer treatment. Polysaccharide-based anticancer prodrugs can be designed to endow derivatives with new bioresponse, targeting, or environmental triggering properties or to combine molecules with synergistic therapeutic effect. Over the years, a variety of synthetic protocols have been set up to conjugate anticancer drugs to the polysaccharide backbone via specific linkages or through spacers which convey to the conjugates selective drug-delivery properties. Furthermore, the intrinsic antitumor activity and cell-targeting properties of few polysaccharides represent an additional value to the final therapeutic systems. Anticancer drugs with different pharmacodynamic, pharmacokinetic, and physicochemical properties have been successfully conjugated to various natural and semisynthetic polysaccharides highlighting the interesting perspectives for exploitation of new promising anticancer polymer therapeutics.

show abstract

Section: Dextranmentioning

confidence: 99%

Section: Methylprednisolone and Tacrolimusmentioning

confidence: 99%

See 1 more Smart Citation

Polysaccharide-Based Anticancer Prodrugs

Caliceti

Salmaso

Bersani

2009

Macromolecular Anticancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…6). Dextran-succinyl-methylprednisolone, having been examined as a soluble conjugate (McLeod et al, 1993(McLeod et al, , 1994Mehvar et al, 2000), releases methylprednisolone and succinyl-prednisolone simultaneously, because succinyl-methylprednisolone is combined with dextran via an ester bond. On the other hand, since SP was combined with Ch in Ch-SP-MS via an amide bond, the binding of the chitosan and succinyl linker was considered to very stable, resulting in the release of Pred alone.…”

Section: In Vitro Drug Releasementioning

confidence: 99%

Preparation and In Vitro Evaluation of Chitosan Microspheres Containing Prednisolone: Comparison of Simple and Conjugate Microspheres

Onishi

Oosegi

Machida

et al. 2005

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 microm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 microm, with the mean diameter of 5 microm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.

show abstract

“…Recently, various chemical modifications (Anderson & Taphouse, 1981;Anderson et al, 1985;Mcleod et al, 1993;Mehvar et al, 2000) or drug delivery systems (Lamprecht et al, 2001a;Nakase et al, 2000;Tozaki et al, 1999a;Tozaki et al, 1999b;Yano et al, 2002) have been developed in order to obtain a highly effective and low-toxic therapeutic system against such IBD. 5-Aminosalicylic acid (5-ASA), and steroidal and non-steroidal anti-inflammatory drugs are frequently chosen for the treatment of IBD (Gionchetti et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Eudragit Coating of Chitosan-Prednisolone Conjugate Microspheres and In Vitro Evaluation of Coated Microspheres

Onishi

Oosegi

Machida

et al. 2007

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37 degrees C. Ch-SP-MS were spherical, with a mean size of 4.5 microm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 microm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.

show abstract

Kinetics of hydrolysis of dextran–methylprednisolone succinate, a macromolecular prodrug of methylprednisolone, in rat blood and liver lysosomes

Cited by 39 publications

References 17 publications

Polysaccharide-Based Anticancer Prodrugs

Polysaccharide-Based Anticancer Prodrugs

Preparation and In Vitro Evaluation of Chitosan Microspheres Containing Prednisolone: Comparison of Simple and Conjugate Microspheres

Eudragit Coating of Chitosan-Prednisolone Conjugate Microspheres and In Vitro Evaluation of Coated Microspheres

Contact Info

Product

Resources

About