FORMULATION, DEVELOPMENT AND IN VITRO EVALUATION OF LAFUTIDINE AND ALOIN-LOADED NANOPARTICLES FOR ENHANCING GASTROPROTECTIVE THERAPY
Abstract
Peptic ulcer disease and other gastric disorders remain major health concerns worldwide due to increasing prevalence associated with stress, Helicobacter pylori infection, excessive alcohol intake, smoking, and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Conventional antiulcer therapies often suffer from limitations such as short gastric residence time, poor bioavailability, frequent dosing, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as promising approaches for improving the therapeutic efficacy of gastroprotective agents through enhanced stability, sustained release, improved mucosal adhesion, and targeted drug delivery. Lafutidine, a second-generation histamine H2 receptor antagonist, exhibits potent acid-suppressive and mucosal protective properties, whereas Aloin, a natural anthraquinone glycoside obtained from Aloe species, possesses antioxidant, anti-inflammatory, cytoprotective, and wound healing activities. The combination of these two agents in nanoparticle systems may provide synergistic gastroprotective effects by simultaneously reducing gastric acid secretion and enhancing mucosal defence mechanisms. This review discusses the formulation strategies, preparation methods, characterization parameters, and in vitro evaluation of Lafutidine and Aloin-loaded nanoparticles. Different nanoparticle systems including polymeric, lipid-based, and mucoadhesive nanoparticles are reviewed with emphasis on their applications in gastroprotective therapy. The review also highlights the importance of physicochemical characterization, drug release studies, stability evaluation, and future perspectives of nanoparticle-based gastroprotective formulations. Overall, Lafutidine and Aloin-loaded nanoparticles represent a promising strategy for improving ulcer healing and enhancing the effectiveness of gastroprotective therapy.
Keywords:
Lafutidine, Aloin, nanoparticles, gastroprotective therapy, gastric ulcer, nanotechnology, managed launch, mucoadhesive drug shippingDOI
https://doi.org/10.5281/zenodo.20502088References
1. Jaiswal, F., Rai, A. K., Wal, P., Wal, A., & Singh, S. P. (2021). Peptic ulcer: a review on etiology, pathogenesis and treatment. Asian Journal of Pharmaceutical Education and Research, 10(4), 1.
2. Vakil, N. (2024). Peptic ulcer disease: a review. Jama, 332(21), 1832-1842.
3. Reshetnyak, V. I., & Reshetnyak, T. M. (2017). Significance of dormant forms of Helicobacter pylori in ulcerogenesis. World journal of gastroenterology, 23(27), 4867.
4. Fokunang, C., Fokunang, E. T., Frederick, K., Ngameni, B., & Ngadjui, B. (2018). Overview of non-steroidal anti-inflammatory drugs (nsaids) in resource limited countries. Moj Toxicol, 4(1), 5-13.
5. Jaiswal, F., Rai, A. K., Wal, P., Wal, A., & Singh, S. P. (2021). Peptic ulcer: a review on etiology, pathogenesis and treatment. Asian Journal of Pharmaceutical Education and Research, 10(4), 1.
6. Sobhani, K., Li, J., & Cortes, M. (2023). Nonsteroidal anti-inflammatory drugs (NSAIDs). In First aid perioperative ultrasound: Acute pain manual for surgical procedures (pp. 127-138). Cham: Springer International Publishing.
7. Patlevič, P., Vašková, J., Švorc Jr, P., Vaško, L., & Švorc, P. (2016). Reactive oxygen species and antioxidant defense in human gastrointestinal diseases. Integrative medicine research, 5(4), 250-258.
8. de Lima, C. A. A., de Lima, R. S., de Souza, J. B., de Souza Graça, A., Thomazzi, S. M., Batista, J. S., & Estevam, C. D. S. (2022). Gastroprotective mechanisms. Peptic ulcer disease-what’s new.
9. Galura, G. M., Chavez, L. O., Robles, A., & McCallum, R. (2019). Gastroduodenal injury: role of protective factors. Current gastroenterology reports, 21(8), 34.
10. Liu, Z., Wang, S., Yang, S., Liu, W., Huo, N., Xu, J., ... & Liu, H. (2025). Bridging Gaps in Oral Mucosa Regeneration: Advances and Challenges. Tissue Engineering Part B: Reviews, 19373368251405708.
11. Choi, W. T., Lauwers, G. Y., & Slavik, T. (2024). Inflammatory disorders of the stomach. Morson and Dawson's Gastrointestinal Pathology, 135-194.
12. Avegno, J., & Carlisle, M. (2016). Evaluating the patient with right upper quadrant abdominal pain. Emergency Medicine Clinics, 34(2), 211-228.
13. Grigorian, A., Lin, M. Y., & de Virgilio, C. (2026). Right Upper Quadrant Pain, Fever, Nausea, and Vomiting. In Surgery: A Case-Based Clinical Review (pp. 271-279). Cham: Springer Nature Switzerland.
14. Müller, A. L. E. (2024). Evaluation of the frequency and necessity of proton-pump-inhibitor therapy in geriatric patients (Doctoral dissertation, Sveučilište u Splitu, Sveučilište u Splitu, Medicinski fakultet).
15. Sano, T., Utsumi, D., Amagase, K., Matsumoto, K., Tominaga, M., Higuchi, K., & Kato, S. (2017). Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties, attenuates 5-fluorouracil-induced intestinal mucositis in mice through activation of extrinsic primary afferent neurons. J Physiol Pharmacol, 68(1), 79-90.
16. Shetty, B., & Vishwanath, M. K. (2022). An expert opinion on antacids: A review of its pharmacological properties and therapeutic efficacy. F1000Research, 11, 1057.
17. Kak, M. (2025). Rebamipide in gastric mucosal protection and healing: An Asian perspective. World Journal of Gastrointestinal Pharmacology and Therapeutics, 16(1), 101753.
18. Rocha, G. R., Lemos, F. F. B., de Oliveira Silva, L. G., Luz, M. S., Santos, G. L. C., Pinheiro, S. L. R., & de Melo, (2025). Overcoming antibiotic-resistant Helicobacter pylori infection: Current challenges and emerging approaches. World Journal of Gastroenterology, 31(10), 102289.
19. Bhatia, S. (2016). Nanoparticles types, classification, characterization, fabrication methods and drug delivery applications. In Natural polymer drug delivery systems: Nanoparticles, plants, and algae (pp. 33-93). Cham: Springer International Publishing.
20. Bai, X., Smith, Z. L., Wang, Y., Butterworth, S., & Tirella, A. (2022). Sustained drug release from smart nanoparticles in cancer therapy: a comprehensive review. Micromachines, 13(10), 1623.
21. Watchorn, J., Clasky, A. J., Prakash, G., Johnston, I. A., Chen, P. Z., & Gu, F. X. (2022). Untangling mucosal drug delivery: engineering, designing, and testing nanoparticles to overcome the mucus barrier. ACS biomaterials science & engineering, 8(4), 1396-1426.
22. Li, M., Liu, Y., & Weigmann, B. (2023). Biodegradable polymeric nanoparticles loaded with flavonoids: A promising therapy for inflammatory bowel disease. International Journal of Molecular Sciences, 24(5), 4454.
23. Kou, E., Zhang, X., Dong, B., Wang, B., & Zhu, Y. (2024). Combination of H1 and H2 histamine receptor antagonists: current knowledge and perspectives of a classic treatment strategy. Life, 14(2), 164.
24. Arin, R. M., Gorostidi, A., Navarro-Imaz, H., Rueda, Y., Fresnedo, O., & Ochoa, B. (2017). Adenosine: direct and indirect actions on gastric acid secretion. Frontiers in Physiology, 8, 737.
25. Pai, U. A., Ravishankar, A. V., Bharadia, L., HR, S., Wadhwa, A., Prajapati, B., & SOANS, S. T. (2025). Evidence-based review by a multidisciplinary team of pediatricians on the use of gastric acid-reducing medications in children: Indian perspectives. Cureus, 17(5).
26. Zhu, L., Guo, J., Liu, Q., Luo, Y., Zhao, J., Zhong, W., & Chen, X. (2023). Lafutidine ameliorates indomethacin-induced small intestinal damage in rats by modifying the intestinal mucosal barrier, inflammation, and microbiota. Pharmacology, 108(3), 286-300.
27. Brahmeswari, P., Sultana, M., & Reddy, C. M. (2022). Formulation and Optimization of Raft Forming Chewable Tablet Containing Lafutidine. Indo-American Journal of Pharma and Bio Sciences, 20(4), 126-134.
28. Zhang, J., Wang, T. X., & Wei, R. N. (2022). Clinical study on Xiaojianzhong capsules combined with lafutidine in treatment of gastric ulcer.
29. Otieno, P. O. (2022). A review on antiplasmodial potential and quantification of aloin and aloe-emodin in aloe vera.
30. Luo, X., Zhang, H., Wei, X., Shi, M., Fan, P., Xie, W., & Xu, N. (2018). Aloin suppresses lipopolysaccharide-induced inflammatory response and apoptosis by inhibiting the activation of NF-κB. Molecules, 23(3), 517.
31. Bawankar, A., & Zawar, L. (2025). Recent advances in phytochemical-based nanoparticles for colon-specific drug delivery. Cellulose chemistry and technology, 59(9-10), 1045-1066.
32. Xiao, J., Chen, S., Chen, Y., & Su, J. (2022). The potential health benefits of aloin from genus Aloe. Phytotherapy Research, 36(2), 873-890.
33. Sah, D. K., Arjunan, A., Lee, B., & Jung, Y. D. (2023). Reactive oxygen species and H. pylori infection: a comprehensive review of their roles in gastric cancer development. Antioxidants, 12(9), 1712.
34. Luo, X., Zhang, H., Wei, X., Shi, M., Fan, P., Xie, W., & Xu, N. (2018). Aloin suppresses lipopolysaccharide-induced inflammatory response and apoptosis by inhibiting the activation of NF-κB. Molecules, 23(3), 517.
35. Jiang, H., Shi, G. F., Fang, Y. X., Liu, Y. Q., Wang, Q., Zheng, X., & Yin, Z. Q. (2022). Aloin A prevents ulcerative colitis in mice by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Phytomedicine, 106, 154403.
36. Tarnawski, A. S., & Ahluwalia, A. (2021). The critical role of growth factors in gastric ulcer healing: the cellular and molecular mechanisms and potential clinical implications. Cells, 10(8), 1964.
37. Donkor, A. M., Donkor, M. N., & Kuubabongnaa, N. (2020). Evaluation of anti-infective potencies of formulated aloin A ointment and aloin A isolated from Aloe barbadensis Miller. BMC chemistry, 14(1), 8.
38. Geszke-Moritz, M., & Moritz, M. (2024). Biodegradable polymeric nanoparticle-based drug delivery systems: comprehensive overview, perspectives and challenges. Polymers, 16(17), 2536.
39. Mehandole, A., Walke, N., Mahajan, S., Aalhate, M., Maji, I., Gupta, U., & Singh, P. K. (2023). Core–shell type lipidic and polymeric nanocapsules: the transformative multifaceted delivery systems. Aaps Pharmscitech, 24(1), 50.
40. Subramanian, P. (2021). Lipid-based nanocarrier system for the effective delivery of nutraceuticals. Molecules, 26(18), 5510.
41. Bayer, I. S. (2022). Recent advances in mucoadhesive interface materials, mucoadhesion characterization, and technologies. Advanced Materials Interfaces, 9(18), 2200211.
42. Bhandare, A., & Nannor, K. M. (2024). Bioavailability in drug design and development: A comprehensive review. World Journal of Pharmaceutical Research, 13(17), 145-168.
43. Idrees, H., Zaidi, S. Z. J., Sabir, A., Khan, R. U., Zhang, X., & Hassan, S. U. (2020). A review of biodegradable natural polymer-based nanoparticles for drug delivery applications. Nanomaterials, 10(10), 1970.
44. Sultana, S., Alzahrani, N., Alzahrani, R., Alshamrani, W., Aloufi, W., Ali, A., & Siddiqui, N. A. (2020). Stability issues and approaches to stabilised nanoparticles-based drug delivery system. Journal of drug targeting, 28(5), 468-486.
45. Chaudhary, S. A., Patel, D. M., Patel, J. K., & Patel, D. H. (2021). Solvent emulsification evaporation and solvent emulsification diffusion techniques for nanoparticles. In Emerging technologies for nanoparticle manufacturing (pp. 287-300). Cham: Springer International Publishing.
46. Miladi, K., Sfar, S., Fessi, H., & Elaissari, A. (2017). Nanoprecipitation process: from particle preparation to in vivo applications. In Polymer Nanoparticles for Nanomedicines: A Guide for their Design, Preparation and Development (pp. 17-53). Cham: Springer International Publishing.
47. Desai, K. G. (2016). Chitosan nanoparticles prepared by ionotropic gelation: An overview of recent advances. Critical Reviews™ in Therapeutic Drug Carrier Systems, 33(2).
48. Sarfraz, R. M., Bashir, S., Mahmood, A., Ahsan, H., Riaz, H., Raza, H., & Yasmeen, T. (2017). Application of various polymers and polymers-based techniques used to improve solubility of poorly water-soluble drugs: A review. Acta Pol. Pharm, 74, 347-356.
49. Malamatari, M., Charisi, A., Malamataris, S., Kachrimanis, K., & Nikolakakis, I. (2020). Spray drying for the preparation of nanoparticle-based drug formulations as dry powders for inhalation. Processes, 8(7), 788.
50. Subramanian, D. A., Langer, R., & Traverso, G. (2022). Mucus interaction to improve gastrointestinal retention and pharmacokinetics of orally administered nano-drug delivery systems. Journal of nanobiotechnology, 20(1), 362.
51. Karmakar, S. A. N. A. T. (2019). Particle size distribution and zeta potential based on dynamic light scattering: Techniques to characterize stability and surface charge distribution of charged colloids. Recent Trends Mater. Phys. Chem, 28, 117-159.
52. Liu, Y., Yang, G., Jin, S., Xu, L., & Zhao, C. X. (2020). Development of high‐drug‐loading nanoparticles. Chem Plus Chem, 85(9), 2143-2157.
53. Gooneh-Farahani, S., Naghib, S. M., & Naimi-Jamal, M. R. (2020). A novel and inexpensive method based on modified ionic gelation for pH-responsive controlled drug release of homogeneously distributed chitosan nanoparticles with a high encapsulation efficiency. Fibers and Polymers, 21(9), 1917-1926.
54. Inkson, B. J. (2016). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for materials characterization. In Materials characterization using nondestructive evaluation (NDE) methods (pp. 17-43). Woodhead publishing.
55. Danaei, M., Kalantari, M., Raji, M., Fekri, H. S., Saber, R., Asnani, G. P., & Taheriazam, A. (2018). Probing nanoliposomes using single particle analytical techniques: Effect of excipients, solvents, phase transition and zeta potential. Heliyon, 4(12).
56. Sindhoor, S. M., Priya, S., & Maxwell, (2018). Formulation and evaluation of novel in situ gel of lafutidine for gastroprotective drug delivery. Asian J Pharm Clin Res, 11(8), 88-94.
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