S-protected Thiolated Chitosan: Synthesis and in Vitro Characterization

Overview

Journal Carbohydr Polym

Specialty Biochemistry

Date 2012 Jul 31

PMID 22839999

Citations 15

Authors

Sarah Dunnhaupt

Jan Barthelmes

Clemens C Thurner

Claudia Waldner

Duangkamon Sakloetsakun

Andreas Bernkop-Schnurch

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Advances in the delivery of anticancer drugs by nanoparticles and chitosan-based nanoparticles.

Jarmila P, Veronika M, Peter M Int J Pharm X. 2024; 8:100281.

PMID: 39297017 PMC: 11408389. DOI: 10.1016/j.ijpx.2024.100281.

BBD Driven Fabrication of Hydroxyapatite Engineered Risedronate Loaded Thiolated Chitosan Nanoparticles and Their In Silico, In Vitro, and Ex Vivo Studies.

Saifi Z, Ralli T, Rizwanullah M, Alam M, Vohora D, Mir S Micromachines (Basel). 2023; 14(12).

PMID: 38138351 PMC: 10745864. DOI: 10.3390/mi14122182.

S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering.

Le-Vinh B, Steinbring C, Le N, Matuszczak B, Bernkop-Schnurch A ACS Appl Mater Interfaces. 2023; 15(34):40304-40316.

PMID: 37594415 PMC: 10472333. DOI: 10.1021/acsami.3c09337.

Development of Novel S-Protective Thiolated-Based Mucoadhesive Tablets for Repaglinide: Pharmacokinetic Study.

Alhakamy N, Raghavendra Naveen N, Gorityala S, Kurakula M, Hosny K, Safhi A Polymers (Basel). 2022; 14(17).

PMID: 36080604 PMC: 9460926. DOI: 10.3390/polym14173529.

Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms.

Abo El-Enin H, Mostafa R, Ahmed M, Naguib I, Abdelgawad M, Ghoneim M Pharmaceutics. 2022; 14(2).

PMID: 35214142 PMC: 8874718. DOI: 10.3390/pharmaceutics14020410.

References

Mortazavi S, Smart J . Factors influencing gel-strengthening at the mucoadhesive-mucus interface. J Pharm Pharmacol. 1994; 46(2):86-90. DOI: 10.1111/j.2042-7158.1994.tb03746.x. View

Barthelmes J, Perera G, Hombach J, Dunnhaupt S, Bernkop-Schnurch A . Development of a mucoadhesive nanoparticulate drug delivery system for a targeted drug release in the bladder. Int J Pharm. 2011; 416(1):339-45. DOI: 10.1016/j.ijpharm.2011.06.033. View

Kafedjiiski K, Krauland A, Hoffer M, Bernkop-Schnurch A . Synthesis and in vitro evaluation of a novel thiolated chitosan. Biomaterials. 2004; 26(7):819-26. DOI: 10.1016/j.biomaterials.2004.03.011. View

Bernkop-Schnurch A, Hornof M, Zoidl T . Thiolated polymers--thiomers: synthesis and in vitro evaluation of chitosan-2-iminothiolane conjugates. Int J Pharm. 2003; 260(2):229-37. DOI: 10.1016/s0378-5173(03)00271-0. View

FORREST H, Walker J . Chemotherapeutic agents of the sulphone type; 2 : 5-disubstituted derivatives of pyridine. J Chem Soc. 1948; :1939-45. DOI: 10.1039/jr9480001939. View

Duchene D, Ponchel G . Principle and investigation of the bioadhesion mechanism of solid dosage forms. Biomaterials. 1992; 13(10):709-14. DOI: 10.1016/0142-9612(92)90132-8. View

Guo J, Ping Q, Jiang G, Dong J, Qi S, Feng L . Transport of leuprolide across rat intestine, rabbit intestine and Caco-2 cell monolayer. Int J Pharm. 2004; 278(2):415-22. DOI: 10.1016/j.ijpharm.2004.03.031. View

Bernkop-Schnurch A, Schwarz V, Steininger S . Polymers with thiol groups: a new generation of mucoadhesive polymers?. Pharm Res. 1999; 16(6):876-81. DOI: 10.1023/a:1018830204170. View

Smart J . The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005; 57(11):1556-68. DOI: 10.1016/j.addr.2005.07.001. View

10.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

11.

Grabovac V, Guggi D, Bernkop-Schnurch A . Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev. 2005; 57(11):1713-23. DOI: 10.1016/j.addr.2005.07.006. View

12.

Marschutz M, Bernkop-Schnurch A . Thiolated polymers: self-crosslinking properties of thiolated 450 kDa poly(acrylic acid) and their influence on mucoadhesion. Eur J Pharm Sci. 2002; 15(4):387-94. DOI: 10.1016/s0928-0987(02)00025-8. View

13.

Leitner V, Walker G, Bernkop-Schnurch A . Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins. Eur J Pharm Biopharm. 2003; 56(2):207-14. DOI: 10.1016/s0939-6411(03)00061-4. View

14.

Bernkop-Schnurch A, Steininger S . Synthesis and characterisation of mucoadhesive thiolated polymers. Int J Pharm. 2000; 194(2):239-47. DOI: 10.1016/s0378-5173(99)00387-7. View

15.

Barrett W, DeGnore J, Konig S, Fales H, Keng Y, Zhang Z . Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry. 1999; 38(20):6699-705. DOI: 10.1021/bi990240v. View

16.

Kast C, Bernkop-Schnurch A . Thiolated polymers--thiomers: development and in vitro evaluation of chitosan-thioglycolic acid conjugates. Biomaterials. 2001; 22(17):2345-52. DOI: 10.1016/s0142-9612(00)00421-x. View

17.

Carlsson J, Drevin H, Axen R . Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent. Biochem J. 1978; 173(3):723-37. PMC: 1185838. DOI: 10.1042/bj1730723. View

18.

Norris R, Brocklehurst K . A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe. Biochem J. 1976; 159(2):245-57. PMC: 1164111. DOI: 10.1042/bj1590245. View

19.

Woodley J . Bioadhesion: new possibilities for drug administration?. Clin Pharmacokinet. 2001; 40(2):77-84. DOI: 10.2165/00003088-200140020-00001. View

20.

Perez-Vilar J, Mabolo R . Gel-forming mucins. Notions from in vitro studies. Histol Histopathol. 2007; 22(4):455-64. DOI: 10.14670/HH-22.455. View