Saliva-Mediated Muco-Adhesive Drug Delivery Systems: A Systematic Review of Polymeric Films and Nanoparticle-Based Approaches
DOI:
https://doi.org/10.36283/ziun-pjmd14-4/093Abstract
Background: Muco-adhesive drug delivery systems utilizing saliva as a physiological medium have gained attention for enhancing drug retention, bioavailability, and patient compliance in oral cavity applications. The physicochemical properties of saliva comprising mucins, enzymes, and electrolytes play a critical role in determining the adhesion, stability, and release behavior of polymer-based drug delivery systems. This systematic study aimed to evaluate the influence of salivary interaction on the performance of muco-adhesive polymeric films and nanoparticles, focusing on their adhesion strength, stability, and controlled drug release characteristics.
Methods: A comprehensive literature search was conducted across PubMed, Scopus, and ScienceDirect for studies published between 2010 and 2025, focusing on polymeric muco-adhesive delivery systems tested under simulated or in vivo salivary conditions. Studies assessing physicochemical parameters such as muco-adhesive strength, drug release kinetics, and polymer–saliva interactions were included. Data extraction and synthesis followed the PRISMA 2020 guidelines.
Results: Across the included studies, chitosan-based nanoparticles demonstrated superior muco-adhesive strength (adhesion times up to 6 hours) and enhanced mucosal permeation compared to synthetic polymers. HPMC–PVP films maintained prolonged contact time and consistent drug release under salivary enzymatic conditions, whereas carbopol-based systems showed variable stability due to pH and enzymatic degradation. Both polymeric films and nanoparticles exhibited improved therapeutic efficacy and patient tolerability when optimized for salivary compatibility.
Conclusion: The findings underscore the importance of tailoring polymer composition and molecular interactions to salivary conditions for achieving efficient muco-adhesive performance. Integrating salivary environment simulations into formulation development can significantly enhance the clinical translation of buccal and sublingual drug delivery systems. Future research should emphasize hybrid polymer-nanoparticle matrices and in vivo correlation studies to refine saliva-mediated muco-adhesive delivery technologies.
References
1. Van De Voorde P, Turner NM, Djakow J, De Lucas N, Martinez-Mejias A, Biarent D, et al. European Resuscitation Council Guidelines 2021: Paediatric Life Support. Resuscitation [Internet]. 2021 Mar 24;161:327–87. Available from: https://doi.org/10.1016/j.resuscitation.2021.02.015
2. Dwivedi YK, Hughes DL, Coombs C, Constantiou I, Duan Y, Edwards JS, et al. Impact of COVID-19 pandemic on information management research and practice: Transforming education, work and life. International Journal of Information Management [Internet]. 2020 Jul 31;55:102211. Available from: https://doi.org/10.1016/j.ijinfomgt.2020.102211
3. Tripathi DK, Alexander A. Novel drug delivery systems. 2020.
4. Pan Z, Zhang X, Xie W, Cui J, Wang Y, Zhang B, et al. Revisited and innovative perspectives of oral ulcer: from biological specificity to local treatment. Frontiers in Bioengineering and Biotechnology [Internet]. 2024 Feb 22;12. Available from: https://doi.org/10.3389/fbioe.2024.1335377
5. Li W, Meng J, Ma X, Lin J, Lu X. Advanced materials for the delivery of vaccines for infectious diseases. Biosafety and Health [Internet]. 2022 Mar 8;4(2):95–104. Available from: https://doi.org/10.1016/j.bsheal.2022.03.002
6. Hu M, Li X. Oral bioavailability and drug delivery: From Basics to Advanced Concepts and Applications. John Wiley & Sons; 2024.
7. Ueda M, Yokota T, Honda M, Lim PN, Osaka N, Makita M, et al. Regulating size of silver nanoparticles on calcium carbonate via ultrasonic spray for effective antibacterial efficacy and sustained release. Materials Science and Engineering C [Internet]. 2021 Mar 31;125:112083. Available from: https://doi.org/10.1016/j.msec.2021.112083
8. Guo Z, Bai Y, Zhang Z, Mei H, Li J, Pu Y, et al. Thermosensitive polymer hydrogel as a physical shield on colonic mucosa for colitis treatment. Journal of Materials Chemistry B [Internet]. 2021 Jan 1;9(18):3874–84. Available from: https://doi.org/10.1039/d1tb00499a
9. Li J, Pradyawong S, Sun XS, Wang D, He Z, Zhong J, et al. Improving adhesion performance of cottonseed protein by the synergy of phosphoric acid and water soluble calcium salts. International Journal of Adhesion and Adhesives [Internet]. 2021 Mar 30;108:102867. Available from: https://doi.org/10.1016/j.ijadhadh.2021.102867
10. Khan BA, Karim F, Khan MK, Haider F, Khan S. Synthesis and characterization of polymeric responsive CMC/Pectin hydrogel films loaded with Tamarix aphylla extract as potential wound dressings. Biocell [Internet]. 2021 Jan 1;45(5):1273–85. Available from: https://doi.org/10.32604/biocell.2021.015323
11. Reddy CM, Krishnan SP, Reddy CB. A Mini-Review on Chitosan Microsphere Drug delivery. Journal of Pharmaceutical Research International [Internet]. 2021 Nov 11;179–86. Available from: https://doi.org/10.9734/jpri/2021/v33i49a33318
12. Dosage Forms - innovation and future perspectives [Internet]. IntechOpen eBooks. 2022. Available from: https://doi.org/10.5772/intechopen.95734
13. Oliveira C, Teixeira JA, Oliveira N, Ferreira S, Botelho CM. Microneedles’ device: design, fabrication, and applications. Macromol—A Journal of Macromolecular Research [Internet]. 2024 May 15;4(2):320–55. Available from: https://doi.org/10.3390/macromol4020019
14. Alam F, Ahmed MA, Jalal A, Siddiquee I, Adury R, Hossain G, et al. Recent progress and challenges of implantable biodegradable biosensors. Micromachines [Internet]. 2024 Mar 30;15(4):475. Available from: https://doi.org/10.3390/mi15040475
15. Group T& F. Cosmetic Formulation: Principles and Practice. CRC Press; 2021.
16. Tasaltin N, Nnamchi PS, Saud S. Advanced functional materials [Internet]. IntechOpen eBooks. 2020. Available from: https://doi.org/10.5772/intechopen.87879
17. Prajapati B, Bhattacharya S, Rodriques P, Pandey V, Haider T, Agrawal P, et al. Advanced drug delivery systems [Internet]. IntechOpen eBooks. 2022. Available from: https://doi.org/10.5772/intechopen.100967
18. Ko A, Liao C. Hydrogel wound dressings for diabetic foot ulcer treatment: Status‐quo, challenges, and future perspectives. BMEMat [Internet]. 2023 Jun 30;1(3). Available from: https://doi.org/10.1002/bmm2.12037
19. Cheng C, Song W, Zhao Q, Zhang H. Halloysite nanotubes in polymer science: purification, characterization, modification and applications. Nanotechnology Reviews [Internet]. 2020 Jan 1;9(1):323–44. Available from: https://doi.org/10.1515/ntrev-2020-0024
20. Fakhruddin K, Hassan R, Khan MUA, Allisha SN, Razak SIA, Zreaqat MH, et al. Halloysite nanotubes and halloysite-based composites for biomedical applications. Arabian Journal of Chemistry [Internet]. 2021 Jul 3;14(9):103294. Available from: https://doi.org/10.1016/j.arabjc.2021.103294
21. Kajdič S, Planinšek O, Gašperlin M, Kocbek P. Electrospun nanofibers for customized drug-delivery systems. Journal of Drug Delivery Science and Technology [Internet]. 2019 Mar 26;51:672–81. Available from: https://doi.org/10.1016/j.jddst.2019.03.038
22. Singh RP, Singh KR. Bionanomaterials: Fundamentals Biomedihb. IOP Publishing Limited; 2021.
23. Knutson DJ, Devine R. Family medicine: PreTest Self-assessment and Review. 2019.
24. Pukale HADDrNHS Dr Sangita Abasaheb Kale, Mr Amol Vasant Deshpande, Ms Kavita Sunil. Comprehensive Textbook of Drug Delivery Systems: As Per PCI New Syllabus Prescribed For DRUG DELIVERY SYSTEMS (MPH 102T). Shashwat Publication; 2025.
25. Lai J, Azad AK, Sulaiman WMAW, Kumarasamy V, Subramaniyan V, Alshehade SA. Alginate-Based Encapsulation Fabrication Technique for Drug delivery: An updated review of particle type, formulation technique, pharmaceutical ingredient, and targeted delivery system. Pharmaceutics [Internet]. 2024 Mar 6;16(3):370. Available from: https://doi.org/10.3390/pharmaceutics16030370
26. Song J, Yuan C, Jiao T, Xing R, Yang M, Adams DJ, et al. Multifunctional antimicrobial biometallohydrogels based on amino acid coordinated Self‐Assembly. Small [Internet]. 2020 Jan 29;16(8). Available from: https://doi.org/10.1002/smll.201907309
27. Singh J, Nayak P. pH‐responsive polymers for drug delivery: Trends and opportunities. Journal of Polymer Science [Internet]. 2023 Aug 23;61(22):2828–50. Available from: https://doi.org/10.1002/pol.20230403
28. Zhang X, Chen G, Zhang H, Shang L, Zhao Y. Bioinspired oral delivery devices. Nature Reviews Bioengineering [Internet]. 2023 Feb 2;1(3):208–25. Available from: https://doi.org/10.1038/s44222-022-00006-4
29. Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduction and Targeted Therapy [Internet]. 2021 Jul 12;6(1). Available from: https://doi.org/10.1038/s41392-021-00658-5
30. Prajapati B, Bhattacharya S, Rodriques P, Pandey V, Haider T, Agrawal P, et al. Advanced drug delivery systems [Internet]. IntechOpen eBooks. 2022. Available from: https://doi.org/10.5772/intechopen.100967
31. Glover RLK, Nyanganyura D, Mufamadi MS, Mulaudzi RB. Green synthesis in nanomedicine and human health. CRC Press; 2021.
32. Cui C, Mei L, Wang D, Jia P, Zhou Q, Liu W. A self-stabilized and water-responsive deliverable coenzyme-based polymer binary elastomer adhesive patch for treating oral ulcer. Nature Communications [Internet]. 2023 Nov 24;14(1). Available from: https://doi.org/10.1038/s41467-023-43571-x
33. Kocira A, Kozłowicz K, Panasiewicz K, Staniak M, Szpunar-Krok E, Hortyńska P. Polysaccharides as Edible Films and Coatings: Characteristics and Influence On Fruit and Vegetable Quality—A Review. Agronomy [Internet]. 2021 Apr 21;11(5):813. Available from: https://doi.org/10.3390/agronomy11050813
34. Fois GR, Vega DL, Pereda A, Terray L, Chardon P, Kolovi S, et al. Simulation of the radiation exposure of microorganisms living in submarine hydrothermal systems using GATE and Geant4-DNA Monte Carlo simulation tools. Book of Abstracts [Internet]. 2023 Jan 1; Available from: https://doi.org/10.21175/rad.abstr.book.2023.39.11
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Pakistan Journal of Medicine and Dentistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/
Metrics
How to Cite
