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Synthesis, characterisation and in vitro evaluation of novel thiolated derivatives of polyallylamine and quaternised polyallylamine.

Ibie, C.O.; Thompson, C.J.; Knott, R.

Authors

C.O. Ibie

C.J. Thompson

R. Knott



Abstract

Polyallylamine (Paa) was quaternised by methylation of its primary amines using methyl iodide to yield quaternised Paa (QPaa). Average level of polymer quaternisation was determined by elemental analysis and was found to be 72 ± 2mol%. Subsequent thiolation of Paa (15kDa) and QPaa using two different thiolation procedures involving carbodiimide-mediated conjugation to N-acetylcysteine (NAC) and modification of the polymers using 2-iminothiolane hydrochloride yielded their respective NAC and 4-thiobutylamidine (TBA) conjugates: Paa-NAC/QPaa-NAC and Paa-TBA/QPaa-TBA. Estimation of the free thiol content of thiomers by iodometric titration showed that Paa-NAC and QPaa-NAC displayed 60 ± 1.2 and 60 ± 4.3μmol free thiol groups per gram polymer, respectively, while Paa-TBA and QPaa-TBA conjugates displayed 490 ± 18 and 440 ± 21μmol free thiol groups per gram polymer, respectively. Assessment of polymer mucoadhesion using the mucin adsorption assay method revealed that Paa-NAC and Paa-TBA had the best mucoadhesive profile both adsorbing >20% more mucin than the parent polymer Paa. However, thiolation of QPaa was not observed to result in a marked improvement in adsorption of mucin. Also, while other thiolated derivatives were stable in Tris/phosphate buffer pH8 with no change in free thiol content, Paa-TBA solutions displayed in situ crosslinking of free thiol groups to a disulphide network which was evident after 2h. These results show that thiolation of Paa enhanced its mucoadhesive properties, with Paa-TBA also exhibiting in situ gelling properties. Hence, these novel thiolated Paa derivatives exhibit properties which may be useful in facilitating transmucosal drug delivery and controlled drug release.

Citation

IBIE, C.O., THOMPSON, C.J. and KNOTT, R. 2015. Synthesis, characterisation and in vitro evaluation of novel thiolated derivatives of polyallylamine and quaternised polyallylamine. Colloid and polymer science [online], 293(6), pages 1737-1748. Available from: https://doi.org/10.1007/s00396-015-3561-4

Journal Article Type Article
Acceptance Date Mar 5, 2015
Online Publication Date Mar 24, 2015
Publication Date Jun 30, 2015
Deposit Date Dec 11, 2017
Publicly Available Date Dec 11, 2017
Journal Colloid and polymer science
Print ISSN 0303-402X
Electronic ISSN 1435-1536
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 293
Issue 6
Pages 1737-1748
DOI https://doi.org/10.1007/s00396-015-3561-4
Keywords Mucodhesion; Thiolation; Quaternisation; Thiomer; In situ crosslinking; Amide; Amidine
Public URL http://hdl.handle.net/10059/2629

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