International Journal of Drug Delivery Technology
Volume 15, Issue 3

Dual-Functional Mucoadhesive Films for Buccal Delivery: Integration of Permeation Enhancers with Smart Polymers for Controlled Release

Rahane Rahulkumar D, Inamdar Saniya N*, Kadam Vaibhav N, Dhumal Prathamesh K

Matoshri Miratai Aher College of pharmacy, Karjule harya, Tal-Parner, Dist-Ahemadnagar, Maharashtra, India 

Received: 10th Nov, 2024; Revised: 17th Jun, 2025; Accepted: 25th Jun, 2025; Available Online: 25th Sep, 2025 

ABSTRACT

Buccal drug delivery is ideal for first-pass drugs, enabling systemic delivery through the buccal mucosa while bypassing hepatic metabolism. This review highlights amphiphilic mucoadhesive films that deliver functionalized permeation enhancers and smart polymers for controlled, sustained release in the buccal environment. Buccal tissue’s layered structure, permeation barriers, saliva washout, and rapid turnover underscore the need for dual-functional systems. These systems, with mucoadhesive properties for retention and enhancers for absorption, improve drug efficacy against mucosal barriers. Smart polymers responsive to pH, temperature, enzymes, and light adjust release profiles to the local environment, enhancing therapy and reducing dosing. Advances in nanocomposite, multilayer, in situ forming films, and 3D-printed and biosensor-integrated films further boost buccal delivery. Nanocomposite films enhance bioavailability, multilayer films ensure stability, in situ films solidify for snug fit, and 3D printing allows personalized designs. Biosensors enable real-time treatment monitoring and adjustments. This review discusses formulation innovations, showing the promise of mucoadhesive and permeation-enhancing technologies for greater therapeutic efficacy, patient compliance, and clinical potential.

Keyword: clinical potential, 3D printing, Buccal drug delivery, nanocomposite, mucoadhesive

How to cite this article: Rahane Rahulkumar D, Inamdar Saniya N, Kadam Vaibhav N, Dhumal Prathamesh K. Dual-Functional Mucoadhesive Films for Buccal Delivery: Integration of Permeation Enhancers with Smart Polymers for Controlled Release. International Journal of Drug Delivery Technology. 2025;15(3):1354-71. doi: 10.25258/ijddt.15.3.58

REFERENCES

  1. Macedo AS, Castro PM, Roque L, Thomé NG, Reis CP, Pintado ME, et al. Novel and revisited approaches in nanoparticle systems for buccal drug delivery. Journal of Controlled Release 2020;320:125–41. https://doi.org/10.1016/j.jconrel.2020.01.006.
  2. JEREMIAH OG. BY ORUIKOR GABRIEL JEREMIAH, DrPH n.d.
  3. Pinto S, Pintado ME, Sarmento B. In vivo, ex vivo and in vitro assessment of buccal permeation of drugs from delivery systems. Expert Opinion on Drug Delivery 2020;17:33–48. https://doi.org/10.1080/17425247.2020.1699913.
  4. Mann G, Gurave PM, Kaul A, Kadiyala KG, Pokhriyal M, Srivastava RK, et al. Polymeric and electrospun patches for drug delivery through buccal route: Formulation and biointerface evaluation. Journal of Drug Delivery Science and Technology 2022;68:103030. https://doi.org/10.1016/j.jddst.2021.103030.
  5. Hua S. Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Front Pharmacol 2020;11:524. https://doi.org/10.3389/fphar.2020.00524.
  6. Walia C, Arya A. Review on Buccal Drug Delivery System 2023;8.
  7. Bhosale N, S. Gudur A, Ramesan R, D. Rane D, D. Arolkar P, S. Darwajkar A, et al. A Comprehensive Review on Buccal Drug Delivery System. AJPT 2023:139–45. https://doi.org/10.52711/2231-5713.2023.00026.
  8. Feitosa RC, Geraldes DC, Beraldo-de-Araújo VL, Costa JSR, Oliveira-Nascimento L. Pharmacokinetic Aspects of Nanoparticle-in-Matrix Drug Delivery Systems for Oral/Buccal Delivery. Front Pharmacol 2019;10:1057. https://doi.org/10.3389/fphar.2019.01057.
  9. Routes AE. Drug absorption, distribution and elimination Pharmacokinetics 2019.
  10. He S, Mu H. Microenvironmental pH Modification in Buccal/Sublingual Dosage Forms for Systemic Drug Delivery. Pharmaceutics 2023;15:637. https://doi.org/10.3390/pharmaceutics15020637.
  11. Hua S. Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration. Front Pharmacol 2019;10:1328. https://doi.org/10.3389/fphar.2019.01328.
  12. Hu S, Pei X, Duan L, Zhu Z, Liu Y, Chen J, et al. A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery. Nat Commun 2021;12:1689. https://doi.org/10.1038/s41467-021-21989-5.
  13. Кilichevna KM, Idievna SG. THE MAIN FUNCTION AND HISTOLOGICAL STRUCTURE OF THE ORAL MUCOSA. Asian Journal of Pharmaceutical and Biological Research 2021;10.
  14. Bruschi ML, De Souza Ferreira SB, Bassi Da Silva J. Mucoadhesive and mucus-penetrating polymers for drug delivery. Nanotechnology for Oral Drug Delivery, Elsevier; 2020, p. 77–141. https://doi.org/10.1016/B978-0-12-818038-9.00011-9.
  15. Groeger S, Meyle J. Oral Mucosal Epithelial Cells. Front Immunol 2019;10:208. https://doi.org/10.3389/fimmu.2019.00208.
  16. Gupta S, Das S, Singh A, Ghosh S. A Brief Review on Bucco-adhesive Drug Delivery System. J Drug Delivery Ther 2021;11:231–5. https://doi.org/10.22270/jddt.v11i4-S.4934.
  17. Wanasathop A, Patel PB, Choi HA, Li SK. Permeability of Buccal Mucosa. Pharmaceutics 2021;13:1814. https://doi.org/10.3390/pharmaceutics13111814.
  18. Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery — A promising option for orally less efficient drugs. Journal of Controlled Release 2006;114:15–40. https://doi.org/10.1016/j.jconrel.2006.04.012.
  19. Wang Y, Pi C, Feng X, Hou Y, Zhao L, Wei Y. The Influence of Nanoparticle Properties on Oral Bioavailability of Drugs. IJN 2020;Volume 15:6295–310. https://doi.org/10.2147/IJN.S257269.
  20. Peterson B, Weyers M, Steenekamp JH, Steyn JD, Gouws C, Hamman JH. Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism. Pharmaceutics 2019;11:33. https://doi.org/10.3390/pharmaceutics11010033.
  21. Nguyen VH, Thuy VN, Van TV, Dao AH, Lee B-J. Nanostructured lipid carriers and their potential applications for versatile drug delivery via oral administration. OpenNano 2022;8:100064. https://doi.org/10.1016/j.onano.2022.100064.
  22. Buya AB, Beloqui A, Memvanga PB, Préat V. Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery. Pharmaceutics 2020;12:1194. https://doi.org/10.3390/pharmaceutics12121194.
  23. Barde HR, Harsulkar DAA. REVIEW: A COMPREHENSIVE STUDY ON BUCCAL PATCHES n.d.;11.
  24. Friedl JD, Walther M, Vestweber PK, Wächter J, Knoll P, Jörgensen AM, et al. SEDDS-loaded mucoadhesive fiber patches for advanced oromucosal delivery of poorly soluble drugs. Journal of Controlled Release 2022;348:692–705. https://doi.org/10.1016/j.jconrel.2022.06.023.
  25. Jingcheng L, Reddy VS, Jayathilaka WADM, Chinnappan A, Ramakrishna S, Ghosh R. Intelligent Polymers, Fibers and Applications. Polymers 2021;13:1427. https://doi.org/10.3390/polym13091427.
  26. Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics 2021;13:1206. https://doi.org/10.3390/pharmaceutics13081206.
  27. Chatterjee S, Chi-leung Hui P. Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application. Molecules 2019;24:2547. https://doi.org/10.3390/molecules24142547.
  28. Dharmayanti C, Gillam TA, Klingler-Hoffmann M, Albrecht H, Blencowe A. Strategies for the Development of pH-Responsive Synthetic Polypeptides and Polymer-Peptide Hybrids: Recent Advancements. Polymers 2021;13:624. https://doi.org/10.3390/polym13040624.
  29. Kamal Z, Su J, Qiu M. Erythrocytes modified (coated) gold nanoparticles for effective drug delivery, 2020, p. 13–29. https://doi.org/10.1016/B978-0-12-816960-5.00002-1.
  30. Pandey M, Choudhury H, Abdul-Aziz A, Bhattamisra SK, Gorain B, Carine T, et al. Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update. Polymers 2020;13:26. https://doi.org/10.3390/polym13010026.
  31. Hanif M, Zaman M, Chaurasiya V. Polymers used in buccal film: a review. Designed Monomers and Polymers 2015;18:105–11. https://doi.org/10.1080/15685551.2014.971389.
  32. Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics 2021;13:1206. https://doi.org/10.3390/pharmaceutics13081206.
  33. Kumar A, Kumar A. Smart Pharmaceutical Formulations of Biopolymeric Materials in Buccal Drug Delivery. Biomedical Materials & Devices 2024. https://doi.org/10.1007/s44174-024-00223-y.
  34. Ammanage A, Rodriques P, Kempwade A, Hiremath R. Formulation and evaluation of buccal films of piroxicam co-crystals. Future Journal of Pharmaceutical Sciences 2020;6:16. https://doi.org/10.1186/s43094-020-00033-1.
  35. Hanif M, Zaman M, Chaurasiya V. Polymers used in buccal film: a review. Designed Monomers and Polymers 2015;18:105–11. https://doi.org/10.1080/15685551.2014.971389.
  36. Kumar A, Kumar A. Smart Pharmaceutical Formulations of Biopolymeric Materials in Buccal Drug Delivery. Biomedical Materials & Devices 2024. https://doi.org/10.1007/s44174-024-00223-y.
  37. Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics 2021;13:1206. https://doi.org/10.3390/pharmaceutics13081206.
  38. Mondal S. Temperature responsive shape memory polyurethanes. Polymer-Plastics Technology and Materials 2021:1–28. https://doi.org/10.1080/25740881.2021.1906903.
  39. Lanzalaco S, Mingot J, Torras J, Alemán C, Armelin E. Recent Advances in Poly(N-isopropylacrylamide) Hydrogels and Derivatives as Promising Materials for Biomedical and Engineering Emerging Applications. Advanced Engineering Materials 2023;25:2201303. https://doi.org/10.1002/adem.202201303.
  40. Huang H, Qi X, Chen Y, Wu Z. Thermo-sensitive hydrogels for delivering biotherapeutic molecules: A review. Saudi Pharmaceutical Journal 2019;27:990–9. https://doi.org/10.1016/j.jsps.2019.08.001.
  41. Qiao S, Wang H. Temperature-responsive polymers: Synthesis, properties, and biomedical applications. Nano Res 2018;11:5400–23. https://doi.org/10.1007/s12274-018-2121-x.
  42. Remiro PDFR, Nagahara MHT, Azoubel RA, Franz-Montan M, d’Ávila MA, Moraes ÂM. Polymeric Biomaterials for Topical Drug Delivery in the Oral Cavity: Advances on Devices and Manufacturing Technologies. Pharmaceutics 2022;15:12. https://doi.org/10.3390/pharmaceutics15010012.
  43. Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics 2021;13:1206. https://doi.org/10.3390/pharmaceutics13081206.
  44. Sobczak M. Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems—State of Knowledge and Future Prospects. IJMS 2022;23:4421. https://doi.org/10.3390/ijms23084421.
  45. Paruchuri BC, Gopal V, Sarupria S, Larsen J. Toward enzyme-responsive polymersome drug delivery. Nanomedicine 2021;16:2679–93.
  46. Das SS, Bharadwaj P, Bilal M, Barani M, Rahdar A, Taboada P, et al. Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis. Polymers 2020;12:1397. https://doi.org/10.3390/polym12061397.
  47. Kaur M, Sharma A, Puri V, Aggarwal G, Maman P, Huanbutta K, et al. Chitosan-Based Polymer Blends for Drug Delivery Systems. Polymers 2023;15:2028. https://doi.org/10.3390/polym15092028.
  48. Wikipedia 2024.
  49. Zelzer M, Todd SJ, Hirst AR, McDonald TO, Ulijn RV. Enzyme responsive materials: design strategies and future developments. Biomater Sci 2012;1:11–39. https://doi.org/10.1039/C2BM00041E.
  50. Stoychev G, Kirillova A, Ionov L. Light‐Responsive Shape‐Changing Polymers. Advanced Optical Materials 2019;7:1900067. https://doi.org/10.1002/adom.201900067.
  51. Alavi SE, Malik L, Matti R, Al-Najafi F, Ebrahimi Shahmabadi H, A. Sharma L. Bioresponsive nanotechnology in pediatric dental drug delivery. Journal of Drug Delivery Science and Technology 2024;93:105436. https://doi.org/10.1016/j.jddst.2024.105436.
  52. Shaw P, Klausen M, Bradley M. A dual action coumarin-camptothecin polymer for light responsive drug release and photodynamic therapy. Polymer Chemistry 2024;15:54–8. https://doi.org/10.1039/D3PY01137B.
  53. Berillo D, Zharkinbekov Z, Kim Y, Raziyeva K, Temirkhanova K, Saparov A. Stimuli-Responsive Polymers for Transdermal, Transmucosal and Ocular Drug Delivery. Pharmaceutics 2021;13:2050. https://doi.org/10.3390/pharmaceutics13122050.
  54. Kumar A, Kumar A. Smart Pharmaceutical Formulations of Biopolymeric Materials in Buccal Drug Delivery. Biomedical Materials & Devices 2024. https://doi.org/10.1007/s44174-024-00223-y.
  55. Ofridam F, Tarhini M, Lebaz N, Gagnière É, Mangin D, Elaissari A. pH ‐sensitive polymers: Classification and some fine potential applications. Polymers for Advanced Techs 2021;32:1455–84. https://doi.org/10.1002/pat.5230.
  56. Tan RYH, Lee CS, Pichika MR, Cheng SF, Lam KY. PH Responsive Polyurethane for the Advancement of Biomedical and Drug Delivery. Polymers 2022;14:1672. https://doi.org/10.3390/polym14091672.
  57. Singh J, Nayak P. pH ‐responsive polymers for drug delivery: Trends and opportunities. Journal of Polymer Science 2023;61:2828–50. https://doi.org/10.1002/pol.20230403.
  58. Amin M, Lammers T, Ten Hagen TLM. Temperature-sensitive polymers to promote heat-triggered drug release from liposomes: Towards bypassing EPR. Advanced Drug Delivery Reviews 2022;189:114503. https://doi.org/10.1016/j.addr.2022.114503.
  59. Yang L, Qiu G, Sun Y, Sun L, Fan X, Han Q, et al. Temperature-Sensitive Sensors Modified with Poly(N-isopropylacrylamide): Enhancing Performance through Tailored Thermoresponsiveness. Molecules 2024;29:3327. https://doi.org/10.3390/molecules29143327.
  60. Kopač T. Mathematical model for characterization of temperature-responsive polymers: A study on the rheological behavior of gelatin and poly(N-isopropylacrylamide). Polymer Testing 2024;133:108402. https://doi.org/10.1016/j.polymertesting.2024.108402.
  61. Ansari MJ, Rajendran RR, Mohanto S, Agarwal U, Panda K, Dhotre K, et al. Poly(N-isopropylacrylamide)-Based Hydrogels for Biomedical Applications: A Review of the State-of-the-Art. Gels 2022;8:454. https://doi.org/10.3390/gels8070454.
  62. Ding Y, Kang Y, Zhang X. Enzyme-responsive polymer assemblies constructed through covalent synthesis and supramolecular strategy. Chem Commun 2015;51:996–1003. https://doi.org/10.1039/C4CC05878J.
  63. Chandrawati R. Enzyme-responsive polymer hydrogels for therapeutic delivery. Exp Biol Med (Maywood) 2016;241:972–9. https://doi.org/10.1177/1535370216647186.
  64. Hu Q, Katti PS, Gu Z. Enzyme-responsive nanomaterials for controlled drug delivery. Nanoscale 2014;6:12273–86. https://doi.org/10.1039/C4NR04249B.
  65. Pirani F. Bio-oriented Micro-and Nano-Structures Based on stimuli-responsive polymers. PhD Thesis. PhD thesis. ScuDo, Politecnico di Torino, 2018.
  66. Huang B, Chen F, Shen Y, Qian K, Wang Y, Sun C, et al. Advances in Targeted Pesticides with Environmentally Responsive Controlled Release by Nanotechnology. Nanomaterials 2018;8:102. https://doi.org/10.3390/nano8020102.
  67. Abdollahi A, Roghani-Mamaqani H, Razavi B, Salami-Kalajahi M. The light-controlling of temperature-responsivity in stimuli-responsive polymers. Polym Chem 2019;10:5686–720. https://doi.org/10.1039/C9PY00890J.
  68. Salih ZT, Al-Mahmood A, Al-Mahmood S. Drug Delivery System Using a Buccal Film. Maaen Journal for Medical Sciences 2023;2. https://doi.org/10.55810/2789-9136.1021.
  69. VIDYASABALE, Khade A, Gadge G, Mahajan U. An Overview on Natural Polymer Based Mucoadhesive Buccal Films for Controlled Drug Delivery. International Journal of Pharmacy Research & Technology (IJPRT) 2020;10:48–57. https://doi.org/10.31838/ijprt/10.01.10.
  70. Safdar R, Omar AA, Arunagiri A, Regupathi I, Thanabalan M. Potential of Chitosan and its derivatives for controlled drug release applications – A review. Journal of Drug Delivery Science and Technology 2019;49:642–59. https://doi.org/10.1016/j.jddst.2018.10.020.
  71. Sandri G, Ruggeri M, Rossi S, Bonferoni MC, Vigani B, Ferrari F. (Trans)buccal drug delivery. Nanotechnology for Oral Drug Delivery, Elsevier; 2020, p. 225–50. https://doi.org/10.1016/B978-0-12-818038-9.00013-2.
  72. Adepu S, Ramakrishna S. Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules 2021;26:5905. https://doi.org/10.3390/molecules26195905.
  73. Chandramouli M, Shivalingappa RP, Vyakaranahal B, Doddamani S, C. S. D, Nagarajaiah SR, et al. Oral Thin-films from Design to Delivery: A Pharmaceutical Viewpoint. Biointerface Research in Applied Chemistry 2023;13. https://doi.org/10.33263/BRIAC132.177.
  74. Balcerak-Woźniak A, Dzwonkowska-Zarzycka M, Kabatc-Borcz J. A Comprehensive Review of Stimuli-Responsive Smart Polymer Materials—Recent Advances and Future Perspectives. Materials 2024;17:4255. https://doi.org/10.3390/ma17174255.
  75. Gao S, Tang G, Hua D, Xiong R, Han J, Shaohua J, et al. Stimuli-responsive bio-based polymeric systems and their applications. Journal of Materials Chemistry B 2019;7. https://doi.org/10.1039/C8TB02491J.
  76. Sikdar P, Uddin MdM, Dip TM, Islam S, Hoque MdS, Dhar AK, et al. Recent advances in the synthesis of smart hydrogels. Mater Adv 2021;2:4532–73. https://doi.org/10.1039/D1MA00193K.
  77. Samir A, Ashour FH, Hakim AAA, Bassyouni M. Recent advances in biodegradable polymers for sustainable applications. Npj Mater Degrad 2022;6:68. https://doi.org/10.1038/s41529-022-00277-7.
  78. da Silva AC, Córdoba de Torresi SI. Advances in Conducting, Biodegradable and Biocompatible Copolymers for Biomedical Applications. Front Mater 2019;6. https://doi.org/10.3389/fmats.2019.00098.
  79. Chiong JA, Tran H, Lin Y, Zheng Y, Bao Z. Integrating Emerging Polymer Chemistries for the Advancement of Recyclable, Biodegradable, and Biocompatible Electronics. Advanced Science 2021;8:2101233. https://doi.org/10.1002/advs.202101233.
  80. Winne J, Leibler L, Prez FED. Dynamic covalent chemistry in polymer networks: a mechanistic perspective. Polymer Chemistry 2019;10:6091–108. https://doi.org/10.1039/C9PY01260E.
  81. Advancements in 3D printing techniques for biomedical applications: a comprehensive review of materials consideration, post processing, applications, and challenges | Discover Materials n.d. https://link.springer.com/article/10.1007/s43939-024-00115-4 (accessed November 4, 2024).
  82. Weems AC, Pérez-Madrigal MM, Arno MC, Dove AP. 3D Printing for the Clinic: Examining Contemporary Polymeric Biomaterials and Their Clinical Utility. Biomacromolecules 2020;21:1037–59. https://doi.org/10.1021/acs.biomac.9b01539.
  83. Ramezani M, Mohd Ripin Z. 4D Printing in Biomedical Engineering: Advancements, Challenges, and Future Directions. JFB 2023;14:347. https://doi.org/10.3390/jfb14070347.
  84. Mobarak MH, Islam MdA, Hossain N, Al Mahmud MdZ, Rayhan MdT, Nishi NJ, et al. Recent advances of additive manufacturing in implant fabrication – A review. Applied Surface Science Advances 2023;18:100462. https://doi.org/10.1016/j.apsadv.2023.100462.
  85. Falahati M, Ahmadvand P, Safaee S, Chang Y-C, Lyu Z, Chen R, et al. Smart polymers and nanocomposites for 3D and 4D printing. Materials Today 2020;40:215–45. https://doi.org/10.1016/j.mattod.2020.06.001.
  86. Imam SS, Hussain A, Altamimi MA, Alshehri S. Four-Dimensional Printing for Hydrogel: Theoretical Concept, 4D Materials, Shape-Morphing Way, and Future Perspectives. Polymers 2021;13:3858. https://doi.org/10.3390/polym13213858.
  87. Kotta S, Aldawsari HM, Badr-Eldin SM, Nair AB, Yt K. Progress in Polymeric Micelles for Drug Delivery Applications. Pharmaceutics 2022;14:1636. https://doi.org/10.3390/pharmaceutics14081636.
  88. Zhu Y, Liu C, Pang Z. Dendrimer-Based Drug Delivery Systems for Brain Targeting. Biomolecules 2019;9:790. https://doi.org/10.3390/biom9120790.
  89. Niculescu A-G, Grumezescu AM. Polymer-Based Nanosystems—A Versatile Delivery Approach. Materials 2021;14:6812. https://doi.org/10.3390/ma14226812.
  90. Venditti I. Morphologies and functionalities of polymeric nanocarriers as chemical tools for drug delivery: A review. Journal of King Saud University - Science 2019;31:398–411. https://doi.org/10.1016/j.jksus.2017.10.004.
  91. De R, Mahata MK, Kim K-T. Structure-Based Varieties of Polymeric Nanocarriers and Influences of Their Physicochemical Properties on Drug Delivery Profiles. Advanced Science 2022;9:2105373. https://doi.org/10.1002/advs.202105373.
  92. Pourshahrestani S, Zeimaran E, Kadri NA, Mutlu N, Boccaccini AR. Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing. Advanced Healthcare Materials 2020;9:2000905. https://doi.org/10.1002/adhm.202000905.
  93. Talebian S, Mehrali M, Taebnia N, Pennisi CP, Kadumudi FB, Foroughi J, et al. Self-Healing Hydrogels: The Next Paradigm Shift in Tissue Engineering? Advanced Science 2019;6:1801664. https://doi.org/10.1002/advs.201801664.
  94. Pan Z, Ye H, Wu D. Recent advances on polymeric hydrogels as wound dressings. APL Bioengineering 2021;5:011504. https://doi.org/10.1063/5.0038364.
  95. Radulescu D-M, Neacsu IA, Grumezescu A-M, Andronescu E. New Insights of Scaffolds Based on Hydrogels in Tissue Engineering. Polymers 2022;14:799. https://doi.org/10.3390/polym14040799.
  96. Rana MM, De La Hoz Siegler H. Evolution of Hybrid Hydrogels: Next-Generation Biomaterials for Drug Delivery and Tissue Engineering. Gels 2024;10:216. https://doi.org/10.3390/gels10040216.
  97. Venkateswaran MR, Khosravi A, Zarepour A, Iravani S, Zarrabi A. Self-healing materials in biomedicine and the circular economy. Environ Sci: Nano 2024;11:2771–802. https://doi.org/10.1039/D4EN00235K.
  98. Khan AA, Kim J-H. Recent advances in materials and manufacturing of implantable devices for continuous health monitoring. Biosensors and Bioelectronics 2024;261:116461. https://doi.org/10.1016/j.bios.2024.116461.
  99. He T, Lee C. Evolving Flexible Sensors, Wearable and Implantable Technologies Towards BodyNET for Advanced Healthcare and Reinforced Life Quality. IEEE Open J Circuits Syst 2021;2:702–20. https://doi.org/10.1109/OJCAS.2021.3123272.
  100. Iravani S. Plant gums for sustainable and eco-friendly synthesis of nanoparticles: recent advances. Inorganic and Nano-Metal Chemistry 2020;50:469–88. https://doi.org/10.1080/24701556.2020.1719155.
  101. Yessa EY, Wientarsih I, Ulum MF, Purwantara B, Amrozi A. The potential of biodegradable polymers: Chitosan, polyethylene glycol, and polycaprolactone as materials for progesterone intravaginal devices. Livestock and Animal Research n.d.;22:11–24.
  102. Osi B, Khoder M, Al-Kinani AA, Alany RG. Pharmaceutical, biomedical and ophthalmic applications of biodegradable polymers (BDPs): literature and patent review. Pharmaceutical Development and Technology 2022;27:341–56. https://doi.org/10.1080/10837450.2022.2055063.
  103. Kulkarni M, Sawant N, Kolapkar A, Huprikar A, Desai ND. Borneol: a Promising Monoterpenoid in Enhancing Drug Delivery Across Various Physiological Barriers. AAPS PharmSciTech 2021;22. https://doi.org/10.1208/s12249-021-01999-8.
  104. Sugumar V, Hayyan M, Madhavan P, Wong WF, Looi CY. Current Development of Chemical Penetration Enhancers for Transdermal Insulin Delivery. Biomedicines 2023;11:664. https://doi.org/10.3390/biomedicines11030664.
  105. Hmingthansanga V, Singh N, Banerjee S, Manickam S, Velayutham R, Natesan S. Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches. Pharmaceutics 2022;14:2818. https://doi.org/10.3390/pharmaceutics14122818.
  106. Yu Y-Q, Yang X, Wu X-F, Fan Y-B. Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications. Front Bioeng Biotechnol 2021;9. https://doi.org/10.3389/fbioe.2021.646554.
  107. De S, Mallik S, Bhattacharya SK, Acharya S, Mondal PS, Rakshit S, et al. IONTOPHORESIS: A FUNCTIONAL APPROACH FOR ENHANCEMENT OF TRANSDERMAL DRUG DELIVERY. IJPBA 2021;9. https://doi.org/10.32553/ijpba.v9i3.190.
  108. Luo Z, Paunović N, Leroux J-C. Physical methods for enhancing drug absorption from the gastrointestinal tract. Advanced Drug Delivery Reviews 2021;175:113814. https://doi.org/10.1016/j.addr.2021.05.024.
  109. Azman M, Sabri AH, Anjani QK, Mustaffa MF, Hamid KA. Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery. Pharmaceuticals 2022;15:975. https://doi.org/10.3390/ph15080975.
  110. Sadeghian I, Heidari R, Sadeghian S, Raee MJ, Negahdaripour M. Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines. European Journal of Pharmaceutical Sciences 2022;169:106094. https://doi.org/10.1016/j.ejps.2021.106094.
  111. Pereira R, Silva SG, Pinheiro M, Reis S, Vale MLD. Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery. Membranes 2021;11:343. https://doi.org/10.3390/membranes11050343.
  112. Department of Pharmaceutics, Siksha “O” Anusandhan University, Bhubaneswar (Odisha), India, Panda P, Sahu A, Department of Pharmaceutics, Siksha “O” Anusandhan University, Bhubaneswar (Odisha), India. Permeation Enhancers for Transdermal Drug Delivery: Strategies and Advancements Focusing Macromolecules. IJAPSR 2023;3:1–11. https://doi.org/10.54105/ijapsr.F4028.103623.
  113. Khan F. Chemical permeation enhancers and their use in transdermal drug delivery n.d.
  114. Jain K. Transdermal Drug Delivery: Technologies, Companies & Markets. 2021.
  115. Desale K, Kuche K, Jain S. Cell-penetrating peptides (CPPs): an overview of applications for improving the potential of nanotherapeutics. Biomater Sci 2021;9:1153–88. https://doi.org/10.1039/D0BM01755H.
  116. Zakany F, Mándity IM, Varga Z, Panyi G, Nagy P, Kovacs T. Effect of the Lipid Landscape on the Efficacy of Cell-Penetrating Peptides. Cells 2023;12:1700. https://doi.org/10.3390/cells12131700.
  117. Fein KC, Gleeson JP, Cochran K, Lamson NG, Doerfler R, Melamed JR, et al. Long-term daily oral administration of intestinal permeation enhancers is safe and effective in mice. Bioengineering & Translational Medicine 2023;8:e10342. https://doi.org/10.1002/btm2.10342.
  118. Navti PD, Pandey A, Nikam AN, Padya BS, Kalthur G, Koteshwara KB, et al. Ionic Liquids Assisted Topical Drug Delivery for Permeation Enhancement: Formulation Strategies, Biomedical Applications, and Toxicological Perspective. AAPS PharmSciTech 2022;23:161. https://doi.org/10.1208/s12249-022-02313-w.
  119. Ofridam F, Tarhini M, Lebaz N, Gagnière É, Mangin D, Elaissari A. pH ‐sensitive polymers: Classification and some fine potential applications. Polymers for Advanced Techs 2021;32:1455–84. https://doi.org/10.1002/pat.5230.
  120. Hmingthansanga V, Singh N, Banerjee S, Manickam S, Velayutham R, Natesan S. Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches. Pharmaceutics 2022;14:2818. https://doi.org/10.3390/pharmaceutics14122818.
  121. Kumar A, Kumar A. Smart Pharmaceutical Formulations of Biopolymeric Materials in Buccal Drug Delivery. Biomedical Materials & Devices 2024. https://doi.org/10.1007/s44174-024-00223-y.
  122. Ghasemiyeh P, Mohammadi-Samani S. Potential of Nanoparticles as Permeation Enhancers and Targeted Delivery Options for Skin: Advantages and Disadvantages. DDDT 2020;Volume 14:3271–89. https://doi.org/10.2147/DDDT.S264648.
  123. Mehrotra S, Bg PK, Nayak PG, Joseph A, Manikkath J. Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins: Overview of Pharmaceutical Strategies to Overcome Absorption Hurdles. Advanced Pharmaceutical Bulletin 2023;14:11. https://doi.org/10.34172/apb.2024.009.
  124. Gao Y, Du L, Li Q, Li Q, Zhu L, Yang M, et al. How physical techniques improve the transdermal permeation of therapeutics: A review. Medicine 2022;101:e29314.
  125. Abbasi M, Heath B. Iontophoresis and electroporation-assisted microneedles: advancements and therapeutic potentials in transdermal drug delivery. Drug Delivery and Translational Research 2024:1–23.
  126. Patel B. PERMEATION ENHANCEMENT AND ADVANCED STRATEGIES: A COMPREHENSIVE REVIEW OF IMPROVED TOPICAL DRUG DELIVERY. International Research Journal of Modernization in Engineering Technology and Science 2024;06:6691–702. https://doi.org/10.56726/IRJMETS57321.
  127. Marathe D, Bhuvanashree VS, Mehta CH, T. A, Nayak UY. Low-Frequency Sonophoresis: A Promising Strategy for Enhanced Transdermal Delivery. Advances in Pharmacological and Pharmaceutical Sciences 2024;2024:1247450. https://doi.org/10.1155/2024/1247450.
  128. Berillo D, Zharkinbekov Z, Kim Y, Raziyeva K, Temirkhanova K, Saparov A. Stimuli-Responsive Polymers for Transdermal, Transmucosal and Ocular Drug Delivery. Pharmaceutics 2021;13:2050. https://doi.org/10.3390/pharmaceutics13122050.
  129. Alex M, Alsawaftah NM, Husseini GA. State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems. Applied Sciences 2024;14:2926. https://doi.org/10.3390/app14072926.
  130. Zhao W, Yu L, Gu Y, Ma W, Wang K, Liang J, et al. Preparation of dual-functional packaging films containing green tea essential oil microcapsules for strawberry preservation: Excellent barrier properties and antioxidant activity. Food Bioscience 2023;56:103279.
  131. Shi X, Wu Y, Tang L, Yin Z, Shi J, Wu X, et al. Dual-functional composite hydrogel platform: A “kill two birds with one stone” strategy for anti-infection and osseointegration in the treatment of infectious bone defects. Chemical Engineering Journal 2024;498:155337. https://doi.org/10.1016/j.cej.2024.155337.
  132. Joshi R, Akram W, Chauhan R, Garud N. Thin Films: A Promising Approach for Drug Delivery System. In: Jesús Villarreal-Gómez L, editor. Drug Carriers, IntechOpen; 2022. https://doi.org/10.5772/intechopen.103793.
  133. Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics 2021;13:1206. https://doi.org/10.3390/pharmaceutics13081206.
  134. Tian B, Liu Y, Liu J. Smart stimuli-responsive drug delivery systems based on cyclodextrin: A review. Carbohydrate Polymers 2021;251:116871. https://doi.org/10.1016/j.carbpol.2020.116871.
  135. Nautiyal U, Saini M. Fast dissolving Buccal film: A comprehensive Review. Asian Pacific Journal of Nursing and Health Sciences 2023;6:11–22.
  136. Shipp L, Liu F, Kerai-Varsani L, Okwuosa TC. Buccal films: A review of therapeutic opportunities, formulations & relevant evaluation approaches. Journal of Controlled Release 2022;352:1071–92. https://doi.org/10.1016/j.jconrel.2022.10.058.
  137. Ehtezazi T, Algellay M, Hardy A. Next Steps in 3D Printing of Fast Dissolving Oral Films for Commercial Production. DDF 2020;14:5–20. https://doi.org/10.2174/1872211314666191230115851.
  138. Singh P. Electrospinning – A Novel Approach to Developing Drug Delivery System n.d.
  139. Lerdsrimongkol J. DEVELOPMENT OF MUCOADHESIVE PATCHES CONTAINING ALPHA- MANGOSTIN FOR APHTHOUS ULCERS 2023.
  140. Shelke PV, Rachh PR, Mankar SD, Gorde PL. Optimization and evaluation of transdermal delivery system for nebivolol hydrochloride. Journal of Applied Pharmaceutical Research 2024;12:21–37.
  141. Alaei S, Omidian H. Mucoadhesion and Mechanical Assessment of Oral Films. European Journal of Pharmaceutical Sciences 2021;159:105727. https://doi.org/10.1016/j.ejps.2021.105727.
  142. Batista P, Castro P, Madureira AR, Sarmento B, Pintado M. Development and Characterization of Chitosan Microparticles-in-Films for Buccal Delivery of Bioactive Peptides. Pharmaceuticals 2019;12:32. https://doi.org/10.3390/ph12010032.
  143. Alves TFR, Rios AC, Da Silva Pontes K, Portella DL, Aranha N, Severino P, et al. Bilayer Mucoadhesive Buccal Film for Mucosal Ulcers Treatment: Development, Characterization, and Single Study Case. Pharmaceutics 2020;12:657. https://doi.org/10.3390/pharmaceutics12070657.
  144. Eleftheriadis GK, Ritzoulis C, Bouropoulos N, Tzetzis D, Andreadis DA, Boetker J, et al. Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation. European Journal of Pharmaceutics and Biopharmaceutics 2019;144:180–92. https://doi.org/10.1016/j.ejpb.2019.09.018.
  145. Amaral BR, Saatkamp RH, Enumo A, Kroth R, Argenta DF, Rebelatto ERL, et al. Development and characterization of thermopressed polyvinyl alcohol films for buccal delivery of benznidazole. Materials Science and Engineering: C 2021;119:111546. https://doi.org/10.1016/j.msec.2020.111546.
  146. Ahmed TA, Bawazir AO, Alharbi WS, Safo MK. Enhancement of Simvastatin ex vivo Permeation from Mucoadhesive Buccal Films Loaded with Dual Drug Release Carriers. IJN 2020;Volume 15:4001–20. https://doi.org/10.2147/IJN.S256925.
  147. 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;13:273. https://doi.org/10.3390/pharmaceutics13020273.
  148. DM WIMS College of Pharmacy, Meppadi Post, Wayanad, Kerala, India, Jose J, Sisira MV, Prasanth MLL, Prasanth CRS, Pradeep PS. Design and Characterization of Buccal Films of Benzocaine for Mouth Ulcer. JOPCR 2021;20:9–17. https://doi.org/10.18579/jopcr/v20i3.ms21062.
  149. Vecchi CF, Said Dos Santos R, Bassi Da Silva J, Rosseto HC, Sakita KM, Svidzinski TIE, et al. Development and in vitro evaluation of buccal mucoadhesive films for photodynamic inactivation of Candida albicans. Photodiagnosis and Photodynamic Therapy 2020;32:101957. https://doi.org/10.1016/j.pdpdt.2020.101957.
  150. Nageeb El-Helaly S, Abd-Elrasheed E, Salim SA, Fahmy RH, Salah S, EL-Ashmoony MM. Green Nanotechnology in the Formulation of a Novel Solid Dispersed Multilayered Core-Sheath Raloxifene-Loaded Nanofibrous Buccal Film; In Vitro and In Vivo Characterization. Pharmaceutics 2021;13:474. https://doi.org/10.3390/pharmaceutics13040474.
  151. Effiong Daniel Ekpa, Umoh Romanus Asuquo, Akpabio Akwaowo Elijah, Sunday Ndiana-Abasi Ime, Uko Anamanyie Ini. The oral film delivery- Application of nanotechnology and potential in medication adherence. GSC Biol and Pharm Sci 2020;11:034–51. https://doi.org/10.30574/gscbps.2020.11.3.0154.
  152. Garavand F, Cacciotti I, Vahedikia N, Rehman A, Apaydın Tarhan Ö, Akbari-Alavijeh S, et al. A comprehensive review on the nanocomposites loaded with chitosan nanoparticles for food packaging. Critical Reviews in Food Science and Nutrition 2020. https://doi.org/10.1080/10408398.2020.1843133.
  153. Uddin MN, Allon A, Roni MA, Kouzi S. Overview and Future Potential of Fast Dissolving Buccal Films as Drug Delivery System for Vaccines. Journal of Pharmacy & Pharmaceutical Sciences 2019;22:388–406. https://doi.org/10.18433/jpps30528.
  154. [Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics 2021;13:1206. https://doi.org/10.3390/pharmaceutics13081206.
  155. Abdelkader H, Fathalla Z, Seyfoddin A, Farahani M, Thrimawithana T, Allahham A, et al. Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants. Advanced Drug Delivery Reviews 2021;177:113957. https://doi.org/10.1016/j.addr.2021.113957.
  156. Yang H, Fang H, Wang C, Wang Y, Qi C, Zhang Y, et al. 3D printing of customized functional devices for smart biomedical systems. SmartMat 2024;5:e1244. https://doi.org/10.1002/smm2.1244.
  157. Pathak K, Saikia R, Das A, Das D, Islam MA, Pramanik P, et al. 3D printing in biomedicine: advancing personalized care through additive manufacturing. Explor Med 2023;4:1135–67. https://doi.org/10.37349/emed.2023.00200.
  158. Jung HH, Lee H, Yea J, Jang K-I. Wearable electrochemical sensors for real-time monitoring in diabetes mellitus and associated complications. Soft Sci 2024;4. https://doi.org/10.20517/ss.2024.02.