title: Alginate-based oral drug delivery system for tuberculosis: pharmacokinetics and therapeutic effects.
abstract: Alginate microparticles were developed as oral sustained delivery carriers for antitubercular drugs in order to improve patient compliance. In the present study, pharmacokinetics and therapeutic effects of alginate microparticle encapsulated antitubercular drugs, i.e. isoniazid, rifampicin and pyrazinamide were examined in guinea pigs. Alginate microparticles containing antitubercular drugs were evaluated for in vitro and in vivo release profiles. These microparticles exhibited sustained release of isoniazid, rifampicin and pyrazinamide for 3-5 days in plasma and up to 9 days in organs. Peak plasma concentration (Cmax), Tmax, elimination half-life (t1/2e) and AUC0- infinity of alginate drugs were significantly higher than those of free drugs. The encapsulation of drug in alginate microparticles resulted in up to a nine-fold increase in relative bioavailability compared with free drugs. Chemotherapeutic efficacy of alginate drug microspheres against experimental tuberculosis showed no detectable cfu values at 1:100 and 1:1000 dilutions of spleen and lung homogenates. Histopathological studies further substantiated these observations, thus suggesting that application of alginate-encapsulated drugs could be useful in the effective treatment of tuberculosis.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012, India.
authors.lastname: Qurrat-ul-Ain
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
authors.forename: G K
authors.initials: GK
authors.lastname: Khuller
authors.forename: S K
authors.initials: SK
authors.lastname: Garg
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004339:Drug Compounding; D005079:Excipients; D006168:Guinea Pigs; D006207:Half-Life; D020100:Hydrogels; D007538:Isoniazid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011718:Pyrazinamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012995:Solubility
chemical_list: D000464:Alginates; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D005079:Excipients; D020100:Hydrogels; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin