S-protected thiolated chitosan: Synthesis and in vitro characterization

• Published in: Carbohydrate polymers Vol. 90; no. 2; pp. 765 - 772
• Main Authors: Dünnhaupt, Sarah, Barthelmes, Jan, Thurner, Clemens C., Waldner, Claudia, Sakloetsakun, Duangkamon, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-10-2012; Elsevier; Elsevier Applied Science Publishers
• Subjects: Applied sciences; Biological and medical sciences; Caco-2 Cells; Chitosan - chemical synthesis; Chitosan - chemistry; Chitosan - pharmacokinetics; Chitosan - pharmacology; Disulfide bond formation; Drug Delivery Systems - adverse effects; Drug Evaluation, Preclinical; Exact sciences and technology; Fertility Agents, Female - administration & dosage; Fertility Agents, Female - pharmacokinetics; General pharmacology; Humans; Leuprolide - administration & dosage; Leuprolide - pharmacokinetics; Medical sciences; Models, Biological; Mucoadhesion; Mucous Membrane - drug effects; Mucous Membrane - metabolism; Natural polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; S-protected thiomers; Stability; Starch and polysaccharides; Structure-Activity Relationship; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacokinetics; Sulfhydryl Compounds - pharmacology; Tablets; Thiomers; Water - chemistry; Water - metabolism; Disulfide bond formation; S-protected thiomers; Stability; Mucoadhesion; Thiomers; Biological properties; Viscoelasticity; Peptides; Mucosa; Cytotoxicity; Drug carrier; Mercaptoacid; Amidation; Organic disulfide; Surface properties; Sulfur containing polymer; Water absorption; Tablet; Release; Nicotinic acid derivatives; Adhesivity; Control release polymer; Experimental study; In vitro; Chemical coupling; Chemical modification; Mucin; Chitosan derivatives; Desintegration; Preparation; Dosage form; Oside polymer; Chitosan; Kinetics; Aqueous solution
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2012.05.028

► Synthesis of a novel mucoadhesive thiolated chitosan with protected thiol groups. ► The novel conjugate exhibited promising mucoadhesive features. ► In vitro cytotoxicity of the new conjugate was evaluated and found to be non-toxic. ► Swelling behavior of the polymer decreased with the increase of protection. ► Enhanced cross linking within the novel conjugate resulted in improved stability.
Purpose of the present study was the generation and evaluation of novel thiolated chitosans, so-named S-protected thiolated chitosans as mucosal drug delivery systems. Stability of all conjugates concerning swelling and disintegration behavior as well as drug release was examined. Mucoadhesive properties were evaluated in vitro on intestinal mucosa. Different thiolated chitosans were generated displaying increasing amounts of attached free thiol groups on the polymer, whereby more than 50% of these thiol groups were linked with 6-mercaptonicotinamide. Based on the implementation of this hydrophobic residue, the swelling behavior was 2-fold decreased, whereas stability was essentially improved. Their mucoadhesive properties were 2- and 14-fold increased compared to corresponding thiolated and unmodified chitosans, respectively. Release studies out of matrix tablets comprising the novel conjugates revealed a controlled release of a model peptide.
Accordingly, S-protected thiomers represent a promising type of mucoadhesive polymers for the development of various mucosal drug delivery systems.