Recent progress in the development of localized drug delivery systems for oral mucosal disorders using mucoadhesive patches

Abstract

Oral diseases are becoming increasingly prevalent worldwide, posing a significant challenge in treating recurrent conditions due to the wet and movable environment of the oral cavity. This environment reduces the residence time of formulations, making it difficult to effectively treat oral diseases. To address this issue, the use of mucoadhesive systems could be a beneficial strategy to prevent accidental swallowing and wash-off. Various approaches have been suggested to provide mucoadhesion and mucosal penetration, including the use of naturally derived or synthetic polymers, bio-inspired materials, or thiomers. These biocompatible oral mucoadhesive systems with strong wet adhesion offer a promising opportunity for drug delivery applications. In this review, we have focused on current oral mucoadhesive systems that improve local treatment of oral diseases. We begin by providing a brief overview of the structural properties of the oral mucosa, permeability considerations, and the mechanism of mucoadhesion. We then provide examples of innovative materials commonly used in oral mucoadhesive drug delivery systems for local therapy.

Keywords

• Oral disease
• mucoadhesion
• mucoadhesive polymers
• thiolated polymers
• mussel inspired polymers

References

1. [1] Reis CSM, Reis JGC, Conceição-Silva F, Valete CM. Oral and oropharyngeal mucosal lesions: clinical-epidemiological study of patients attended at a reference center for infectious diseases. Braz J Otorhinolaryngol. 2016; 90(3). https://doi.org/10.1016/j.bjorl.2024.101396
2. [2] Li Cl, Ren X, Fang X, Luo H, Hua H. Clinical, histological and direct immunofluorescence features in oral mucosal patches striae diseases with malignant potential. J Dent Sci. 2023; 18(3): 1008-1015. https://doi.org/10.1016/j.jds.2022.11.028
3. [3] Habib L, Alyan M, Ghantous Y, Shklover J, Shainsky J, Abu El-Naaj I, Schroeder A. A mucoadhesive patch loaded with freeze-dried liposomes for the local treatment of oral tumors. Drug Deliv Transl Res. 2023; 13(5):1228-1245. https://doi.org/10.1007/s13346-022-01224-4
4. [4] Sankar V, Hearnden V., Hull K, Juras DV, Greenberg M, Kerr A, Thornhill M. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis. 2011; 17(s1):73-84. https://doi.org/10.1111/j.1601-0825.2011.01793.x
5. [5] Mao Y, Xu Z, He Z, Wang J, Zhu Z. Wet-adhesive materials of oral and maxillofacial region: From design to application. Chin Chem Lett. 2023; 34(1): 107461. https://doi.org/10.1016/j.cclet.2022.04.059
6. [6] Pagano C, Giovagnoli S, Perioli L, Tiralti MC, Ricci M. Development and characterization of mucoadhesive-thermoresponsive gels for the treatment of oral mucosa diseases. Eur J Pharm Sci. 2020; 142: 105125. https://doi.org/10.1016/j.ejps.2019.105125
7. [7] Xu J, Strandman S, Zhu JXX, Barralet J, Cerruti M. Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery. Biomaterials. 2015; 37: 395-404. https://doi.org/10.1016/j.biomaterials.2014.10.024
8. [8] Fonseca-Santos B, Chorilli M. An overview of polymeric dosage forms in buccal drug delivery: State of art, design of formulations and their in vivo performance evaluation. Mater Sci Eng C Mater Biol Appl. 2018; 86: 129-143. https://doi.org/10.1016/j.msec.2017.12.022

9. [9] Bruschi ML, De Freitas O. Oral Bioadhesive Drug Delivery Systems. Drug Dev Ind Pharm. 2005; 31(3): 293-310. https://doi.org/10.1081/DDC-52073
10. [10] Huang Y, Leobandung W, Foss A, Peppas NA. Molecular aspects of muco- and bioadhesion. J Control Release. 2000; 65(1-2):63-71. https://doi.org/10.1016/S0168-3659(99)00233-3
11. [11] Vielmuth F. Anatomy of the Oral Mucosa. In E. Schmidt (Ed.), Diseases of the Oral Mucosa. 2021; (pp. 5-19). Springer International Publishing. https://doi.org/10.1007/978-3-030-82804-2_2
12. [12] Hearnden V, Sankar V, Hull K, Juras DV, Greenberg M, Kerr AR, Thornhill MH. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev. 2012; 64(1): 16-28. https://doi.org/10.1016/j.addr.2011.02.008
13. [13] Şenel S. An overview of physical, microbiological and ımmune barriers of oral mucosa. Int J Mol Sci. 2021; 22(15): 7821. https://doi.org/10.3390/ijms22157821
14. [14] Rathbone MJ, Senel S, Pather I. Oral Mucosal Drug Delivery and Therapy (M. J. Rathbone, S. Senel, & I. Pather, Eds.). 2015. Springer US.
15. [15] Harris D, Robinson JR. Drug Delivery via the Mucous Membranes of the Oral Cavity. J Pharm Sci. 1992; 81(1): 1-10. https://doi.org/10.1002/jps.2600810102
16. [16] Salamatmiller N, Chittchang M, Johnston T. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev. 2005; 57(11): 1666-1691. https://doi.org/10.1016/j.addr.2005.07.003
17. [17] Paderni C, Compilato D, Giannola LI, Campisi G. Oral local drug delivery and new perspectives in oral drug formulation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 114(3): e25-e34. https://doi.org/10.1016/j.oooo.2012.02.016
18. [18] Mathew AK. Oral local drug delivery: An overview. Pharm Pharmacol Res. 2015; 3(1): 1-6.
19. [19] Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery — A promising option for orally less efficient drugs. J Control Release. 2006; 114(1): 15-40. https://doi.org/10.1016/j.jconrel.2006.04.012
20. [20] Smart JD. Buccal Drug Delivery. Expert Opin Drug Deliv. 2005; 2(3): 507-517. https://doi.org/10.1517/17425247.2.3.507
21. [21] Samiraninezhad N, Asadi K, Rezazadeh H, Gholami A. Using chitosan, hyaluronic acid, alginate, and gelatin-based smart biological hydrogels for drug delivery in oral mucosal lesions: A review. Int J Biol Macromol. 2023; 252: 126573. https://doi.org/10.1016/j.ijbiomac.2023.126573
22. [22] Yan C, Pochan DJ. Rheological properties of peptide-based hydrogels for biomedical and other applications. Chem Soc Rev. 2010; 39(9): 3528. https://doi.org/10.1039/b919449p
23. [23] Prezotti FG, Siedle I, Boni FI, Chorilli M, Müller I, Cury BSF. Mucoadhesive films based on gellan gum/pectin blends as potential platform for buccal drug delivery. Pharm Dev Technol. 2020; 25(2): 159-167. https://doi.org/10.1080/10837450.2019.1682608
24. [24] Fonseca-Santos B, Bonifacio BV, Baub TM, Gremiao MPD, Chorilli M. In-situ gelling liquid crystal mucoadhesive vehicle for curcumin buccal administration and ıts potential application in the treatment of oral candidiasis. J Biomed Nanotechnol. 2019; 15(6): 1334-1344. https://doi.org/10.1166/jbn.2019.2758
25. [25] Ritu MG, Mohd I, Sunny S, Neeraj G. A clinical perspective on mucoadhesive buccal drug delivery systems. J Biomed Res. 2014; 28(2): 81. https://doi.org/10.7555/JBR.27.20120136
26. [26] Montero-Padilla S, Velaga S, Morales JO. Buccal dosage forms: General considerations for pediatric patients. AAPS PharmSciTech. 2017; 18(2): 273-282. https://doi.org/10.1208/s12249-016-0567-2
27. [27] Jaipal A, Pandey MM, Charde SY, Sadhu N, Srinivas A, Prasad RG. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies. Drug Deliv. 2016; 23(2): 452-458. https://doi.org/10.3109/10717544.2014.917388
28. [28] Smart JD. Theories of Mucoadhesion. In : Mucoadhesive Materials and Drug Delivery Systems. 2014; 159-174. https://doi.org/https://doi.org/10.1002/9781118794203.ch07
29. [29] Bandi SP, Bhatnagar S, Venuganti VVK. Advanced materials for drug delivery across mucosal barriers. Acta Biomater. 2021; 119: 13-29. https://doi.org/10.1016/j.actbio.2020.10.031
30. [30] Murgia X, Loretz B, Hartwig O, Hittinger M, Lehr CM. The role of mucus on drug transport and its potential to affect therapeutic outcomes. Adv Drug Deliv Rev. 2018; 124: 82-97. https://doi.org/10.1016/j.addr.2017.10.009
31. [31] Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci. 2011; 11(6): 748-764. https://doi.org/10.1002/mabi.201000388
32. [32] Kharenko EA, Larionova NI, Demina NB. Mucoadhesive drug delivery systems (Review). Pharm Chem J. 2009; 43(4): 200-208. https://doi.org/10.1007/s11094-009-0271-6
33. [33] Puri V, Sharma A, Maman P, Rathore N, Singh I. Overview of mucoadhesive biopolymers for buccal drug delivery systems. Int J Appl Pharm. 2019; 18-29. https://doi.org/10.22159/ijap.2019v11i6.35438
34. [34] Pathak K, Malviya R. Introduction, Theories and Mechanisms of Bioadhesion. In K. L. Mittal, I. S. Bakshi, & J. K. Narang (Eds.), Bioadhesives in Drug Delivery. 2020; (1 ed., pp. 1-27). Wiley.
35. [35] Porwal A, Pathak K. Bioadhesion: Fundamentals and Mechanisms. In K. L. Mittal & S. Neogi (Eds.), Adhesives in Biomedical Applications. 2023; (1 ed., pp. 71-98). Wiley.
36. [36] Chatterjee B, Amalina N, Sengupta P, Mandal UK. Mucoadhesive polymers and their mode of action: A recent update. J Appl Pharm Sci. 2017; 7(5): 195-203. http://dx.doi.org/10.7324/JAPS.2017.70533
37. [37] Boddupalli B, Mohammed ZK, Nath R, Banji D. Mucoadhesive drug delivery system: An overview. J Adv Pharm Technol Res. 2010; 1(4): 381. https://doi.org/10.4103/0110-5558.76436 [38] Smart J. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005; 57(11): 1556-1568. https://doi.org/10.1016/j.addr.2005.07.001
38. [39] Sandesh ASJ, Ankur C. Bioadhesive or mucoadhesive drug delivery system: A potential alternative to conventional therapy. J Drug Deliv Ther. 2019; 9(4): 858 - 867. https://doi.org/https://doi.org/10.22270/jddt.v9i4-A.3708
39. [40] Vasquez-Martínez N, Guillen D, Moreno-Mendieta SA, SanchezS, Rodríguez-Sanoja R. The role of mucoadhesion and mucopenetration in the ımmune response ınduced by polymer-based mucosal adjuvants. Polymers (Basel). 2023; 15(7): 1615. https://doi.org/10.3390/polym15071615
40. [41] Shaikh R, Raj ST, Garland M, Woolfson A, Donnelly R. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011; 3(1): 89. https://doi.org/10.4103/0975-7406.76478
41. [42] Madsen F. A rheological examination of the mucoadhesive/mucus interaction: the effect of mucoadhesive type and concentration. J Control Release. 1998; 50(1-3): 167-178. https://doi.org/10.1016/S0168-3659(97)00138-7
42. [43] Bartkowiak A, Rojewska M, Hyla K, Zembrzuska J, Prochaska K. Surface and swelling properties of mucoadhesive blends and their ability to release fluconazole in a mucin environment. Colloids Surf B Biointerfaces. 2018; 172: 586-593. https://doi.org/10.1016/j.colsurfb.2018.09.014
43. [44] Vroman L. Effect of adsorbed proteins on the wettability of hydrophilic and hydrophobic solids. Nature. 1962; 196(4853): 476-477. https://doi.org/10.1038/196476a0
44. [45] Saraswathi B, Balaji A, Umashankar M. Polymers in mucoadhesive drug delivery system-latest updates. Int J Pharm Pharm Sci. 2013; 5(3): 423-430.
45. [46] Hao J, Heng PWS. Buccal Delivery Systems. Drug Dev Ind Pharm. 2003; 29(8): 821-832. https://doi.org/10.1081/DDC-120024178
46. [47] Chinna RP, Madhusudan RY. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru. 2011; 9(6).
47. [48] Singh I, Rana V. Enhancement of Mucoadhesive Property of Polymers for Drug Delivery Applications. Rev Adhes Adhes. 2013; 1(2): 271-290. https://doi.org/10.7569/RAA.2013.097307
48. [49] Zhu Z, Zhai Y, Zhang N, Leng D, Ding P. The development of polycarbophil as a bioadhesive material in pharmacy. Asian J Pharm Sci. 2013; 8(4): 218-227. https://doi.org/10.1016/j.ajps.2013.09.003
49. [50] Cook SL, Bull SP, Methven L, Parker JK, Khutoryanskiy VV. Mucoadhesion: A food perspective. Food Hydrocoll. 2017; 72: 281-296. https://doi.org/10.1016/j.foodhyd.2017.05.043
50. [51] Serra L, Domenech J, Peppas NA. Engineering design and molecular dynamics of mucoadhesive drug delivery systems as targeting agents. Eur J Pharm Biopharm. 2009; 71(3): 519-528. https://doi.org/10.1016/j.ejpb.2008.09.022
51. [52] Mura P, Maestrelli F, Cirri M, Mennini N. Multiple roles of chitosan in mucosal drug delivery: An updated review. Mar Drugs. 2022; 20(5): 335. https://doi.org/10.3390/md20050335
52. [53] Kumar A, Vimal, A. Why Chitosan? From properties to perspective of mucosal drug delivery. Int J Biol Macromol. 2016; 91: 615-622. https://doi.org/10.1016/j.ijbiomac.2016.05.054
53. [54] Ryu JH, Choi JS, Park E, Eom MR, Jo S, Lee MS, Lee H. Chitosan oral patches inspired by mussel adhesion. J Control Release. 2020; 317: 57-66. https://doi.org/10.1016/j.jconrel.2019.11.006.
54. [55] Onnainty R, Onida B, Paez P, Longhi M, Barresi A, Granero G. Targeted chitosan-based bionanocomposites for controlled oral mucosal delivery of chlorhexidine. Int J Pharm. 2016; 509(1-2): 408-418. https://doi.org/10.1016/j.ijpharm.2016.06.011
55. [56] Aksungur P, Sungur A, Unal S, .skit AB, Squier CA, .enel S. Chitosan delivery systems for the treatment of oral mucositis: in vitro and in vivo studies. J Control Release. 2004; 98(2): 269-279. https://doi.org/10.1016/j.jconrel.2004.05.002
56. [57] Pornpitchanarong C, Rojanarata T, Opanasopit P, Ngawhirunpat T, Patrojanasophon P. Catechol-modified chitosan/hyaluronic acid nanoparticles as a new avenue for local delivery of doxorubicin to oral cancer cells. Colloids Surf B Biointerfaces. 2020; 196: 111279. https://doi.org/10.1016/j.colsurfb.2020.111279
57. [58] Abo-shady AZ, Elkammar H, Elwazzan VS, Nasr M. Formulation and clinical evaluation of mucoadhesive buccal films containing hyaluronic acid for treatment of aphthous ulcer. J Drug Deliv Sci Technol. 2020; 55: 101442. https://doi.org/10.1016/j.jddst.2019.101442
58. [59] Nolan A, Baillie C, Badminton J, Rudralingham M, Seymour RA. The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med. 2006; 35(8): 461-465. https://doi.org/10.1111/j.1600-0714.2006.00433.x
59. [60] Alkhalidi HM., Hosny KM, Rizg WY. Oral gel loaded by fluconazole.sesame oil nanotransfersomes: development, optimization, and assessment of antifungal activity. Pharmaceutics. 2020; 13(1): 27. https://doi.org/10.3390/pharmaceutics13010027
60. [61] Paris AL, Caridade S, Colomb E, Bellina M, Boucard E, Verrier B, Monge C. Sublingual protein delivery by a mucoadhesive patch made of natural polymers. Acta Biomater. 2021; 128: 222-235. https://doi.org/10.1016/j.actbio.2021.04.024
61. [62] Pornpitchanarong C, Rojanarata T, Opanasopit P, Ngawhirunpat T, Patrojanasophon P. Clotrimazole nanosuspensions-loaded hyaluronic acid-catechol/polyvinyl alcohol mucoadhesive films for oral candidiasis treatment. J Drug Deliv Sci Technol. 2020; 60: 101927. https://doi.org/10.1016/j.jddst.2020.101927
62. [63] Zhu T, Yu X, Yi X, Guo X, Li L, Hao Y, Wang W. Lidocaine-loaded hyaluronic acid adhesive microneedle patch for oral mucosal topical anesthesia. Pharmaceutics. 2022; 14(4): 686. https://doi.org/10.3390/pharmaceutics14040686
63. [64] Li XJ, Li Y, Meng Y, Pu XQ, Qin JW, Xie R, Chu LY. Composite dissolvable microneedle patch for therapy of oral mucosal diseases. Biomaterials Adv. 2022; 139: 213001. https://doi.org/10.1016/j.bioadv.2022.213001
64. [65] Cecen B, Bal-Ozturk A, Yasayan G, Alarcin E, Kocak P, Tutar R, Miri AK. Selection of natural biomaterials for micro-tissue and organ-on-chip models. J Biomed Mater Res A. 2022; 110(5): 1147-1165. https://doi.org/10.1002/jbm.a.37353
65. [66] Shtenberg Y, Goldfeder M, Prinz H, Shainsky J, Ghantous Y, El-Naaj IA, Bianco-Peled H. Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery. Int J Biol Macromol. 2018; 111: 62-69. https://doi.org/10.1016/j.ijbiomac.2017.12.137
66. [67] Lee KY, Mooney DJ. Alginate: Properties and biomedical applications. Prog Polym Sci. 2012; 37(1): 106-126. https://doi.org/10.1016/j.progpolymsci.2011.06.003
67. [68] Özbaş Z, Özkahraman B, Akgüner ZP, Bal-Öztürk A. Evaluation of modified pectin/alginate buccal patches with enhanced mucoadhesive properties for drug release systems: In-vitro and ex-vivo study. J Drug Deliv Sci Technol. 2022; 67:102991. https://doi.org/10.1016/j.jddst.2021.102991
68. [69] Alarçin E. Pectin/poly(vinylpyrrolidone) composite sponges as wound dressings for delivery of silver sulfadiazine. J Res Pharm. 2022; 26(4): 900-910. https://doi.org/10.29228/jrp.188
69. [70] Villanova JCO, Ayres E, Oréfice RL. Design, characterization and preliminary in vitro evaluation of a mucoadhesive polymer based on modified pectin and acrylic monomers with potential use as a pharmaceutical excipient. Carbohydr Polym. 2015; 121: 372-381. https://doi.org/10.1016/j.carbpol.2014.12.052
70. [71] Laurén P, Paukkonen H, Lipiäinen T, Dong Y, Oksanen T, Räikkönen H, Laaksonen T. Pectin and mucin enhance the bioadhesion of drug loaded nanofibrillated cellulose films. Pharm Res. 2018; 35(7):145. https://doi.org/10.1007/s11095-018-2428-z
71. [72] Özkahraman B, Torkay G, Özbaş Z, Bal-Öztürk A. The effect of vitamin C in the formulation of pectin/thiolated alginate buccal adhesive patches: In vitro and Ex vivo evaluation. Int J Adhes Adhes. 2023; 120: 103276. https://doi.org/10.1016/j.ijadhadh.2022.103276
72. [73] Yaşayan G, Alarçin E, Bal-Öztürk A, Avci-Adali M. Natural polymers for wound dressing applications. In: Studies in Natural Products Chemistry. 2022; (Vol. 74, pp. 367-441). Elsevier. https://doi.org/10.1016/B978-0-323-91099-6.00004-9
73. [74] Jovanović M, Tomić N, Cvijić S, Stojanović D, Ibrić S, Uskoković P. mucoadhesive gelatin buccal films with propranolol hydrochloride: evaluation of mechanical, mucoadhesive, and biopharmaceutical properties. Pharmaceutics. 2021; 13(2): 273. https://doi.org/10.3390/pharmaceutics13020273
74. [75] Davoudi Z, Rabiee M, Houshmand B, Eslahi N, Khoshroo K, Rasoulianboroujeni M, Tayebi L. Development of chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis. Drug Dev Ind Pharm. 2018; 44(1): 40-55. https://doi.org/10.1080/03639045.2017.1371738
75. [76] Dekina S, Romanovska I, Ovsepyan A, Tkach , Muratov E. Gelatin/carboxymethyl cellulose mucoadhesive films with lysozyme: Development and characterization. Carbohydr Polym. 2016; 147: 208-215. https://doi.org/10.1016/j.carbpol.2016.04.006
76. [77] Russo E, Selmin F, Baldassari S, Gennari CGM, Caviglioli G, Cilurzo F, Parodi B. A focus on mucoadhesive polymers and their application in buccal dosage forms. J Drug Deliv Sci Technol. 2016; 32: 113-125. https://doi.org/10.1016/j.jddst.2015.06.016
77. [78] Fini A, Bergamante V, Ceschel GC. Mucoadhesive gels designed for the controlled release of chlorhexidine in the oral cavity. Pharmaceutics. 2011; 3(4): 665-679. https://doi.org/10.3390/pharmaceutics3040665
78. [79] Timur SS, Yüksel S, Akca G, Şenel S. Localized drug delivery with mono and bilayered mucoadhesive films and wafers for oral mucosal infections. Int J Pharm. 2019; 559: 102-112. https://doi.org/10.1016/j.ijpharm.2019.01.029
79. [80] Ho HN, Le HH, Le TG, Duong THA, Ngo VQT, Dang C T, Nguyen CN. Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery. Int J Biol Macromol. 2022; 194: 1010-1018. https://doi.org/10.1016/j.ijbiomac.2021.11.161
80. [81] Barry B, Meyer M. The rheological properties of carbopol gels I. Continuous shear and creep properties of carbopol gels. Int J Pharm. 1979; 2(1): 1-25. https://doi.org/10.1016/0378-5173(79)90025-5
81. [82] Syed MA, Hanif S, Ain NU, Syed HK, Zahoor AF, Khan IU, Sultan MH. Assessment of binary agarose–carbopol buccal gels for mucoadhesive drug delivery: Ex vivo and ın vivo characterization. Molecules. 2022; 27(20): 7004 https://doi.org/10.3390/molecules27207004
82. [83] Caviglioli G, Baldassari S, Cirrincione P, Russo E, Parodi B, Gatti P, Drava G. An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose. Int J Pharm. 2013; 458(1): 74-82. https://doi.org/10.1016/j.ijpharm.2013.10.014
83. [84] Li T, Bao Q, Shen J, Lalla RV, Burgess DJ. Mucoadhesive in situ forming gel for oral mucositis pain control. Int J Pharm. 2020; 580: 119238. https://doi.org/10.1016/j.ijpharm.2020.119238
84. [85] Tamburic S, Craig DQM. An investigation into the rheological, dielectric and mucoadhesive properties of poly(acrylic acid) gel systems. Pharm Res. 1995; 37(1-2): 59-68. https://doi.org/10.1016/0168-3659(95)00064-F
85. [86] Özkahraman B, Özbaş Z, Yaşayan G, Akgüner ZP, Yarımcan F, Alarçin E, Bal‐Öztürk A. Development of mucoadhesive modified kappa-carrageenan/pectin patches for controlled delivery of drug in the buccal cavity. J Biomed Mater Res B Appl Biomater. 2022; 110(4): 787-798. https://doi.org/10.1002/jbm.b.34958
86. [87] Bal-Öztürk A, Torkay G, Alarçin E, Özbaş Z, Özkahraman B. The effect of thiol functional groups on bovine serum albumin/chitosan buccal mucoadhesive patches. J Drug Deliv Sci Technol. 2022; 74: 103493. https://doi.org/10.1016/j.jddst.2022.103493
87. [88] Laffleur F, Küppers P. Adhesive alginate for buccal delivery in aphthous stomatitis. Carbohydr Res. 2019; 477: 51-57. https://doi.org/10.1016/j.carres.2019.03.009
88. [89] Naz K, Shahnaz G, Ahmed N, Qureshi NA, Sarwar HS, Imran M, Khan GM. Formulation and ın vitro characterization of thiolated buccoadhesive film of fluconazole. AAPS PharmSciTech. 2017; 18(4): 1043-1055. https://doi.org/10.1208/s12249-016-0607-y
89. [90] Rohrer J, Partenhauser A, Zupančič O, Leonavičiūtė G, Podričnik S, Bernkop-Schnürch A. Thiolated gelatin films: Renaissance of gelatin as sustained intraoral dosage form. Eur Polym J. 2017; 87: 48-59. https://doi.org/10.1016/j.eurpolymj.2016.11.028
90. [91] Bhatia M, Ahuja M, Mehta H. Thiol derivatization of Xanthan gum and its evaluation as a mucoadhesive polymer. Carbohydr Polym. 2015; 131: 119-124. https://doi.org/10.1016/j.carbpol.2015.05.049
91. [92] Laffleur F, Leder N, Barthelmes J. In vitro evaluation of thio-poly acrylic acid for intraoral delivery. Drug Deliv. 2016; 23(6): 2065-2073. https://doi.org/10.3109/10717544.2015.1122673.
92. [93] Frank BP, Belfort G. Adhesion of Mytilus edulis Foot Protein 1 on Silica: Ionic Effects on Biofouling. Biotechnol Prog. 2002; 18(3): 580-586. https://doi.org/10.1021/bp010140s
93. [94] Silverman HG, Roberto FF. Understanding marine mussel adhesion. Mar Biotechnol (NY). 2007; 9(6): 661-681. https://doi.org/10.1007/s10126-007-9053-x
94. [95] Han L, Lu X, Liu K, Wang K, Fang L, Weng LT, Li Z. Mussel-inspired adhesive and tough hydrogel based on nanoclay confined dopamine polymerization. ACS nano. 2017; 11(3): 2561-2574. https://doi.org/10.1021/acsnano.6b05318
95. [96] Rischka K, Richter K, Hartwig A, Kozielec M, Slenzka K, Sader R, Grunwald I. Bio-inspired Polyphenolic Adhesives for Medical and Technical Applications. In J. Von Byern & I. Grunwald (Eds.), Biological Adhesive Systems. 2010; (pp. 201-211). Springer Vienna.
96. [97] Shi C, Chen X, Zhang Z, Chen Q, Shi D, Kaneko D. Mussel inspired bio-adhesive with multi-interactions for tissue repair. J Biomater Sci Polym Ed. 2020; 31(4): 491-503. https://doi.org/10.1080/09205063.2019.1702276
97. [98] Li Y, Cheng J, Delparastan P, Wang H, Sigg SJ, DeFrates KG, Messersmith PB. Molecular design principles of Lysine-DOPA wet adhesion. Nat Commun. 2020; 11(1): 3895. https://doi.org/10.1038/s41467-020-17597-4
98. [99] Gowda AHJ, Bu Y, Kudina O, Krishna KV, Bohara RA, Eglin D, Pandit A. Design of tunable gelatin-dopamine based bioadhesives. Int J Biol Macromol. 2020; 164: 1384-1391. https://doi.org/10.1016/j.ijbiomac.2020.07.195
99. [100] Hu S, Pei X, Duan L, Zhu Z, Liu Y, Chen J, Wang J. A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery. Nat Commun. 2021; 12(1): 1689. https://doi.org/10.1038/s41467-021-21989-5.