Thiomer

Thiolated polymers – designated thiomers – are functional polymers used in biotechnology product development with the intention to prolong mucosal drug residence time and to enhance absorption of drugs. The name thiomer was coined by Andreas Bernkop-Schnürch in 2000.[1] Thiomers have thiol bearing side chains.[2][3] Sulfhydryl ligands of low molecular mass are covalently bound to a polymeric backbone consisting of mainly biodegradable polymers, such as chitosan,[4][5] hyaluronic acid,[6] cellulose derivatives,[7] pullulan,[8][9] starch,[10] gelatin,[11] polyacrylates,[12] cyclodextrins,[13][14] or silicones.[15]

Thiomers exhibit properties potentially useful for non-invasive drug delivery via oral, ocular, nasal, vesical, buccal and vaginal routes. Thiomers show also potential in the field of tissue engineering and regenerative medicine. Various thiomers such as thiolated chitosan[16] and thiolated hyaluronic acid[17] are commercialy available as scaffold materials. Thiomers can be directly compressed to tablets or given as solutions.[18][19] In 2012, a second generation of thiomers – called "preactivated" or "S-protected" thiomers – were introduced.[20]

In contrast to thiomers of the first generation, preactivated thiomers are stable towards oxidation and display comparatively higher mucoadhesive and permeation enhancing properties.[21] Approved thiomer products for human use are for example eyedrops for treatment of dry eye syndrome or adhesive gels for treatment of nickel allergy.[22]

  1. ^ Bernkop-Schnürch, A; Scholler, S; Biebel, RG (2000). "Development of controlled drug release systems based on polymer-cysteine conjugates". J. Control. Release. 66 (1): 39–47. doi:10.1016/S0168-3659(99)00256-4. PMID 10708877.
  2. ^ Bernkop-Schnürch, Andreas; Schwarz, Veronika; Steininger, Sonja (1999). "Polymers with Thiol Groups: A New Generation of Mucoadhesive Polymers". Pharm. Res. 16 (11): 876–881. doi:10.1016/j.addr.2005.07.002. PMID 16176846.
  3. ^ Bernkop-Schnürch, Andreas; Steininger, Sonja (2000). "Synthesis and characterisation of mucoadhesive thiolated polymers". Int. J. Pharm. 194 (2): 239–247. doi:10.1016/S0378-5173(99)00387-7. PMID 10692648.
  4. ^ Bernkop-Schnürch, A; Hornof, M; Guggi, D (2004). "Thiolated chitosans". Eur. J. Pharm. Biopharm. 57 (1): 9–17. doi:10.1016/S0939-6411(03)00147-4. PMID 14729077.
  5. ^ Zhang, Z; Lin, S; Yan, Y; You, X; Ye, H (2021). "Enhanced efficacy of transforming growth factor-β1 loaded an injectable cross-linked thiolated chitosan and carboxymethyl cellulose-based hydrogels for cartilage tissue engineering". J Biomater Sci Polym ed. 32 (18): 2402–2422. doi:10.1080/09205063.2021.1971823. PMID 34428384. S2CID 237290902.
  6. ^ Zheng Shu, X; Liu, Y; Palumbo, FS; Luo, Y; Prestwich, GD (2004). "In situ crosslinkable hyaluronan hydrogels for tissue engineering". Biomaterials. 7–8 (7–8): 1339–1348. doi:10.1016/j.biomaterials.2003.08.014. PMID 14643608.
  7. ^ Laffleur, F; Bacher, L; Vanicek, S; Menzel, C; Muhammad, I (2016). "Next generation of buccadhesive excipient: Preactivated carboxymethyl cellulose". Int J Pharm. 500 (1–2): 120–127. doi:10.1016/j.ijpharm.2016.01.012. PMID 26773600.
  8. ^ Leonaviciute, G; Suchaoin, W; Matuszczak, B; Lam, HT; Mahmood, A; Bernkop-Schnürch, A (2016). "Preactivated thiolated pullulan as a versatile excipient for mucosal drug targeting". Carbohydr Polym. 151: 743–751. doi:10.1016/j.carbpol.2016.06.005. PMID 27474621.
  9. ^ Priya, SS; Rekha, MR (2016). "Disulphide cross linked pullulan based cationic polymer for improved gene delivery and efflux pump inhibition". Colloids Surf B. 146: 879–887. doi:10.1016/j.colsurfb.2016.07.013. PMID 27459414.
  10. ^ Jelkmann, M; Bonengel, S; Menzel, C; Markovic, S; Bernkop-Schnürch, A (2018). "New perspectives of starch: Synthesis and in vitro assessment of novel thiolated mucoadhesive derivatives". Int J Pharm. 546 (1–2): 70–77. doi:10.1016/j.ijpharm.2018.05.028. PMID 29758345. S2CID 44071363.
  11. ^ Duggan, S; O'Donovan, O; Owens, E; Cummins, W; Hughes, H (2015). "Synthesis of mucoadhesive thiolated gelatin using a two-step reaction process". Eur. J. Pharm. Biopharm. 91: 75–81. doi:10.1016/j.ejpb.2015.01.027. PMID 25661588.
  12. ^ Hornof, M; Weyenberg, W; Ludwig, A; Bernkop-Schnürch, A (2003). "Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans". J. Control. Release. 89 (3): 419–428. doi:10.1016/S0168-3659(03)00135-4. PMID 12737844.
  13. ^ Ijaz, M; Ahmad, M; Akhtar, N; Laffleur, F; Bernkop-Schnürch, A (2016). "Thiolated α-cyclodextrin: the invisible choice to prolong ocular drug residence time". J. Pharm. Sci. 105 (9): 2848–2854. doi:10.1016/j.xphs.2016.04.021. PMID 27233687.
  14. ^ Ijaz, M; Prantl, M; Lupo, N; Laffleur, F; Hussain Asim, M; Matuszczak, B; Bernkop-Schnürch, A (2017). "Development of pre-activated α-cyclodextrin as a mucoadhesive excipient for intra-vesical drug delivery". Int. J. Pharm. 534 (1–2): 339–347. doi:10.1016/j.ijpharm.2017.10.054. PMID 29111098.
  15. ^ Partenhauser, A; Laffleur, F; Rohrer, J; Bernkop-Schnürch, A (2015). "Thiolated silicone oil: synthesis, gelling and mucoadhesive properties". Acta Biomater. 16: 169–177. doi:10.1016/j.actbio.2015.01.020. PMC 4362771. PMID 25660565.
  16. ^ Federer, C; Kurpiers, M; Bernkop-Schnürch, A (2021). "Thiolated Chitosans: A Multi-talented Class of Polymers for Various Applications". Biomacromolecules. 22 (1): 24–56. doi:10.1021/acs.biomac.0c00663. PMC 7805012. PMID 32567846.
  17. ^ Griesser, J; Hetényi, G; Bernkop-Schnürch, A (2018). "Thiolated Hyaluronic Acid as Versatile Mucoadhesive Polymer: From the Chemistry Behind to Product Developments-What Are the Capabilities?". Polymers. 10 (3): 243. doi:10.3390/polym10030243. PMC 6414859. PMID 30966278.
  18. ^ Grosso, R; de-Paz, MV (2021). "Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies-Reviewing Thiomers from Chitosan and Hyaluronic Acid". Pharmaceutics. 13 (6): 854. doi:10.3390/pharmaceutics13060854. PMC 8227107. PMID 34201403.
  19. ^ Hock, N; Racaniello, GF; Aspinall, S; Denora, N; Khutoryanskiy, V; Bernkop-Schnürch, A (2022). "Thiolated Nanoparticles for Biomedical Applications: Mimicking the Workhorses of our Body". Adv Sci (Weinh). 9 (1): 2102451. doi:10.1002/advs.202102451. PMC 8728822. PMID 34773391.
  20. ^ Iqbal, J; Shahnaz, G; Dünnhaupt, S; Müller, C; Hintzen, F; Bernkop-Schnürch, A (2012). "Preactivated thiomers as mucoadhesive polymers for drug delivery". Biomaterials. 33 (5): 1528–1535. doi:10.1016/j.biomaterials.2011.10.021. PMC 3260419. PMID 22118819.
  21. ^ Ijaz, M; Bernkop-Schnürch, A (2015). "Preactivated thiomers: their role in drug delivery". Expert Opin Drug Deliv. 12 (8): 1269–1281. doi:10.1517/17425247.2015.1005598. PMID 25604394. S2CID 28514814.
  22. ^ Federer, C; Kurpiers, M; Bernkop-Schnürch, A (2021). "Thiolated Chitosans: A Multi-talented Class of Polymers for Various Applications". Biomacromolecules. 22 (1): 24–56. doi:10.1021/acs.biomac.0c00663. PMC 7805012. PMID 32567846.