title: Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity.
abstract: Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections.
  
  
  CONCLUSIONS
  In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are biodegradable, cytocompatible and anti-mycobacterial in nature.
authors.affiliation: Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Queeny
authors.initials: Q
authors.lastname: Dasgupta
authors.affiliation: Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India; Department of Chemical Engineering, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Giridhar
authors.initials: G
authors.lastname: Madras
authors.affiliation: Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India; Department of Materials Engineering, Indian Institute of Science, Bangalore 560012, India. Electronic address: kchatterjee@materials.iisc.ernet.in.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Chatterjee
mesh_terms: D010131:Aminosalicylic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D063566:Biodegradable Plastics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D009161:Mycobacterium / Q000254:growth & development*; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D041681:NIH 3T3 Cells; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D063566:Biodegradable Plastics; D003692:Delayed-Action Preparations; D011091:Polyesters; D010131:Aminosalicylic Acid
keywords: Biodegradable polymers; Controlled release; Mycobacteria; Polyesters; p-aminosalicylic acid