Mucosal Drug Delivery System Current Trends and Future Direction

Abstract

In recent years, mucosal drug delivery systems have drawn a lot of attention because of their potential to increase patient compliance and therapeutic efficacy. These systems provide a non-invasive substitute for traditional oral and parenteral techniques by administering medications through mucosal membranes, including the buccal, sublingual, nasal, pulmonary, vaginal, rectal, and ocular channels. The ability to avoid first-pass hepatic metabolism, which increases bioavailability and permits a quick commencement of action, is one of the main benefits. Mucoadhesive gels, nanoparticles, films, liposomes, and in situ gelling systems are some of the novel mucosal drug delivery platforms made possible by recent developments in polymer science, nanotechnology, and drug formulation techniques. These methods facilitate targeted therapy, regulate drug release, and improve mucosal retention. To further maximize drug absorption and reduce systemic side effects, intelligent delivery methods that react to physiological cues like pH, temperature, and enzymes are also developing. Despite their potential, mucosal drug delivery methods encounter a number of difficulties, such as restricted permeability for macromolecules, enzymatic degradation, and variations in mucosal physiology. Novel approaches include the use of Nano carriers, Bioadhesive polymers, and permeation enhancers are being used in ongoing research to solve these problems. Mucosal drug delivery has the potential to transform gene delivery, peptide and protein therapies, and chronic illness treatment approaches in the future. Future developments are anticipated to be fuelled by integration with 3D printing, AI, and personalised medicine, which will make these systems more effective and patient-focused.

Introduction

Mucosal drug delivery, which uses the epithelial linings of organs like the mouth, nose, lungs, vagina, and rectum, is increasingly important due to its advantages over traditional oral delivery. These routes bypass the gastrointestinal tract and first-pass metabolism, allowing faster onset, better bioavailability, and suitability for drugs with limited oral absorption. Mucosal membranes are highly permeable and vascularized, enabling systemic absorption, while facilitating self-administration and improving patient compliance, especially in pediatric and elderly populations.

Advances in pharmaceutical sciences have introduced novel delivery systems—such as mucoadhesive gels, patches, nanoparticles, and in situ gels—that enhance drug retention, penetration, and sustained release. Nanotechnology and stimuli-responsive polymers further improve targeting and controlled drug release. Emerging technologies like 3D printing enable personalized dosing devices tailored to patient needs.

Each mucosal site (oral, nasal, pulmonary, vaginal, rectal, ocular) has unique anatomical and physiological characteristics influencing drug absorption and formulation design. While mucosal delivery offers many benefits, challenges remain, including enzymatic degradation, limited absorption area, and mucociliary clearance. Strategies like permeation enhancers and enzyme inhibitors are used to overcome these barriers.

Several mucosal drug delivery products are commercially available, and regulatory bodies such as the FDA and EMA provide guidelines to ensure safety, efficacy, and quality. Future directions focus on mucosal vaccines, biologics delivery, gene therapy, AI-driven formulation design, wearable devices, and sustainable materials to enhance efficacy and patient-centric therapies.

Conclusion

Mucosal drug delivery systems, which provide non-invasive, patient-friendly substitutes for conventional drug administration routes, constitute a revolutionary approach in contemporary pharmaceutics. These methods take advantage of the distinct physiological and anatomical properties of mucosal tissues to offer targeted therapy, enhanced bioavailability, and a quick onset of action. Thanks to developments in biotechnology, nanotechnology, and materials science, mucosal delivery has developed into an advanced platform that can handle a range of therapeutic issues. Mucoadhesive systems, in situ gels, and nanoparticulate carriers are examples of innovations that have greatly improved therapeutic efficacy, permeability, and retention. Successful case studies and commercially available medicines in the oral, nasal, vaginal, and ocular routes show how adaptable and useful these systems are in therapeutic settings. Although there are still issues with guaranteeing patient acceptability, safety, and consistency, regulatory bodies have started to promote the creation and approval of such innovative formulations through organised guidelines. In the future, mucosal drug delivery is expected to be essential for the delivery of vaccines, gene treatments, and biologics, especially in personalised and preventive medicine. These technologies will be even more efficient and customisable when integrated with 3D printing, artificial intelligence, and smart materials. Mucosal drug delivery has the potential to be a key component of next-generation pharmaceutical care as research and technology develop, offering safer, more convenient, and more effective treatment choices for a variety of illnesses.

References

[1] Aungst, B. J. (2000). Intestinal permeation enhancers. Journal of Pharmaceutical Sciences, 89(4), 429–442. [2] Bende, G., & Rathore, A. S. (2017). Quality by design in mucosal drug delivery. BioPharm International, 30(3), 26–32. [3] Bernkop-Schnürch, A. (2005). Thiomers: A new generation of mucoadhesive polymers. Advanced Drug Delivery Reviews, 57(11), 1569–1582. [4] Boateng, J. S., Matthews, K. H., Stevens, H. N. E., & Eccleston, G. M. (2008). Wound healing dressings and drug delivery systems: A review. Journal of Pharmaceutical Sciences, 97(8), 2892–2923. [5] Brain, J. D. (1970). The uptake of particles by the rat tracheal epithelium. Experimental Cell Research, 61(2), 473–483. [6] Carvalho, F. C., Bruschi, M. L., Evangelista, R. C., & Gremião, M. P. D. (2010). Mucoadhesive drug delivery systems. Brazilian Journal of Pharmaceutical Sciences, 46(1), 1–17. [7] Cevher, E., Taha, M. A., Orhan, E., & Mülaz?mo?lu, L. (2010). Bioadhesive drug delivery systems: A review. FABAD Journal of Pharmaceutical Sciences, 35(4), 215–234. [8] Costantino, H. R., Illum, L., Brandt, G., Johnson, P. H., & Quay, S. C. (2007). Intranasal delivery: Physicochemical and therapeutic aspects. International Journal of Pharmaceutics, 337(1–2), 1–24. [9] Dürig, T., & Fassihi, R. (2002). Guar-based monolithic matrix systems: Effect of ionizable and non-ionizable polymers on gel dynamics and release rate. Journal of Controlled Release, 80(1–3), 45–56. [10] Edsman, K., & Hägerström, H. (2005). Pharmaceutical applications of mucoadhesive delivery systems. European Journal of Pharmaceutics and Biopharmaceutics, 60(3), 447–455. [11] Ghosh, T., Rathi, R., & Ghosh, A. (2005). Bioadhesive drug delivery systems: A review. Tropical Journal of Pharmaceutical Research, 4(1), 319–329. [12] Hickey, A. J. (2001). Pharmaceutical inhalation aerosol technology. CRC Press. [13] Illum, L. (2003). Nasal drug delivery—possibilities, problems and solutions. Journal of Controlled Release, 87(1–3), 187–198. [14] Jain, R. A. (2000). The manufacturing techniques of various drug-loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials, 21(23), 2475–2490. [15] Jiang, H., Wang, L., & Wang, S. (2012). Advances in mucosal vaccine delivery. Vaccine, 30(2), 236–241. [16] Lehr, C. M. (2000). Lectin-mediated drug delivery: The second generation of bioadhesives. Journal of Controlled Release, 65(1–2), 19–29. [17] Mahalingam, R., & Suh, H. W. (2017). Mucosal delivery of biologics: Challenges and opportunities. Therapeutic Delivery, 8(4), 223–231. [18] Marttin, E., Schipper, N. G., Verhoef, J. C., & Merkus, F. W. (1998). Nasal mucociliary clearance as a factor in nasal drug delivery. Advanced Drug Delivery Reviews, 29(1–2), 13–38. [19] Morimoto, K., Yamaguchi, H., Nakai, Y., & Nagai, T. (1985). Application of polyacrylic acid to nasal drug delivery systems. Journal of Pharmaceutical Sciences, 74(12), 1280–1283. [20] Morishita, M., & Peppas, N. A. (2006). Is the oral route possible for peptide and protein drug delivery? Drug Discovery Today, 11(19–20), 905–910. [21] Moulari, B., Beduneau, A., Pellequer, Y., & Lamprecht, A. (2008). Nanoparticle targeting to inflamed tissues of gastrointestinal tract. Current Drug Delivery, 5(3), 223–230. [22] Muranishi, S. (1990). Absorption enhancers. Critical Reviews in Therapeutic Drug Carrier Systems, 7(1), 1–33. [23] Park, C. R., & Munday, D. L. (2002). Development and evaluation of a biphasic buccal adhesive tablet for nicotine replacement therapy. Drug Development and Industrial Pharmacy, 28(6), 643–652. [24] Patel, V. F., Liu, F., & Brown, M. B. (2011). Advances in oral transmucosal drug delivery. Journal of Controlled Release, 153(2), 106–116. [25] Perrie, Y., & Rades, T. (2012). Pharmaceutical Nanotechnology. CRC Press. [26] Ponchel, G., & Irache, J. M. (1998). Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Advanced Drug Delivery Reviews, 34(2–3), 191–219. [27] Prego, C., Torres, D., Fernandez-Megia, E., Novoa-Carballal, R., Quinoa, E., Riguera, R., & Alonso, M. J. (2006). Chitosan–PEG nanocapsules as new carriers for oral peptide delivery: effect of chitosan pegylation degree. Journal of Controlled Release, 111(3), 299–308. [28] Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D., Järvinen, T., & Savolainen, J. (2008). Prodrugs: design and clinical applications. Nature Reviews Drug Discovery, 7(3), 255–270. [29] Schipper, N. G., Verhoef, J. C., & Merkus, F. W. (1991). The nasal mucociliary clearance: relevance to nasal drug delivery. Pharmaceutical Research, 8(7), 807–814. [30] Shojaei, A. H. (1998). Buccal mucosa as a route for systemic drug delivery: a review. Journal of Pharmacy and Pharmaceutical Sciences, 1(1), 15–30. [31] Smart, J. D. (2005). The basics and underlying mechanisms of mucoadhesion. Advanced Drug Delivery Reviews, 57(11), 1556–1568. [32] Sudhakar, Y., Kuotsu, K., & Bandyopadhyay, A. K. (2006). Buccal bioadhesive drug delivery—a promising option for orally less efficient drugs. Journal of Controlled Release, 114(1), 15–40. [33] Sungthongjeen, S., Pitaksuteepong, T., Somsiri, A., & Sriamornsak, P. (2003). Mucoadhesive buccal tablets of chlorpheniramine maleate. Formulation, in vitro and in vivo performance. Drug Development and Industrial Pharmacy, 29(9), 955–966. [34] Taylor, K. M. G., & Aulton, M. E. (2017). Aulton\'s Pharmaceutics: The Design and Manufacture of Medicines. Elsevier Health Sciences. [35] Torchilin, V. P. (2005). Recent advances with liposomes as pharmaceutical carriers. Nature Reviews Drug Discovery, 4(2), 145–160. [36] Van der Merwe, S. M., Verhoef, J. C., Verheijden, J. H. M., & Merkus, F. W. (2004). The nasal delivery of insulin. Drug Discovery Today, 9(9), 442–451. [37] Vllasaliu, D., Thanou, M., Stolnik, S., & Garnett, M. (2014). Intracellular pathways of epithelial uptake and transport of polystyrene nanoparticles. Biomacromolecules, 15(11), 4361–4370. [38] Wang, J., & Weller, C. L. (2006). Recent advances in extraction of nutraceuticals from plants. Trends in Food Science & Technology, 17(6), 300–312. [39] Whitehead, K., Karr, N., & Mitragotri, S. (2008). Safe and effective permeation enhancers for oral drug delivery. Pharmaceutical Research, 25(8), 1782–1788. [40] Wu, W., Wang, Y., & Que, L. (2019). Oral transmucosal drug delivery for diabetes management. Journal of Controlled Release, 303, 47–59.

Copyright

Copyright © 2025 Ms. Shubhangee K. Patil , Ms. Darshana S. Saner, Mr. Shoaib Pinjari. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.