We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Research Article

Prophylactic and therapeutic role of catechin-loaded poly(D,L-lactic-co-glycolic acid) nanocapsules in gastric ulcer by in vitro and in vivo approach

    Anirban Roy

    *Author for correspondence: Tel.: +91 983 611 6930;

    E-mail Address: anirbanroy1234@gmail.com

    Department of Food Technology & Biochemical Engineering, Jadavpur University, Kolkata, West Bengal, 700032, India

    &
    Runu Chakraborty

    Department of Food Technology & Biochemical Engineering, Jadavpur University, Kolkata, West Bengal, 700032, India

    Published Online:https://doi.org/10.2217/nnm-2022-0267

    Background: Gastric ulcer develops from imbalance of gastro-aggressive and protective factors. As existing drugs have adverse effects, use of natural products is in continuous expansion. In this study, we prepared nanoformulation with catechin and polylactide-co-glycolide to provide a sustained, controlled and targeted delivery. Materials & methods: Detailed characterization and toxicity study of nanoparticles were done on cells and Wistar rats. The comparative actions of free compound and nanocapsule were investigated in vitro and in vivo during treatment of gastric injury. Results: Nanocatechin improved bioavailability, reduced gastric damage at a significantly lower dose (2.5 mg/kg) by safeguarding from reactive oxygen species, restored mitochondrial integrity and downregulated MMP-9 and other inflammatory mediators. Conclusion: Nanocatechin is a better alternative for preventing and healing gastric ulcers.

    Plain language summary

    Gastric ulcer, a chronic disease, has a widespread effect on the global populace. Side effects become an issue with available drugs, so natural products are getting acceptance. A promising nanodrug has been designed with catechin, the primary component of green tea, to offer enhanced potency at a lower dose. Toxicity and efficacy studies on laboratory rats have shown its suitability for biological use. In our experimental model of gastric ulcer in rats, nanocatechin was given as drug. It showed improved absorption and relatively fast healing without any adverse impacts. Molecular-level research demonstrated its role in restoring mitochondrial integrity. Thus, it may be an alternative choice for treating stomach ulcers in the clinical setting.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic ulcer disease: a brief review of conventional therapy and herbal treatment options. J. Clin. Med. 8(2), 179 (2019).
    • 2. Xie X, Ren K, Zhou Z et al. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol. 22(1), 58 (2022).
    • 3. Tai FWD, McAlindon ME. Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clin. Med. (Lond.) 21(2), 131–134 (2021).
    • 4. Gunaydin C, Bilge SS. Effects of nonsteroidal anti-inflammatory drugs at the molecular level. Eurasian J. Med. 50(2), 116–121 (2018).
    • 5. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 135(1), 41–60 (2008). • Depicts the molecular details of NSAID-associated gastric mucosal injury and the inherent defence.
    • 6. Danielak A, Wallace JL, Brzozowski T, Magierowski M. Gaseous mediators as a key molecular targets for the development of gastrointestinal-safe anti-inflammatory pharmacology. Front. Pharmacol. 12, 657457 (2021).
    • 7. Bernatoniene J, Kopustinskiene DM. The role of catechins in cellular responses to oxidative stress. Molecules 23(4), 965 (2018).
    • 8. Fan FY, Sang LX, Jiang M. Catechins and their therapeutic benefits to inflammatory bowel disease. Molecules 22(3), 484 (2017).
    • 9. Cai ZY, Li XM, Liang JP et al. Bioavailability of tea catechins and its improvement. Molecules 23(9), 2346 (2018).
    • 10. Stillhart C, Vučićević K, Augustijns P et al. Impact of gastrointestinal physiology on drug absorption in special populations – an UNGAP review. Eur. J. Pharm. Sci. 147, 105280 (2020).
    • 11. Patra JK, Das G, Fraceto LF et al. Nano based drug delivery systems: recent developments and future prospects. J. Nanobiotechnol. 16(1), 71 (2018).
    • 12. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20(2), 101–124 (2021).
    • 13. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 94(3), 909–950 (2014).
    • 14. Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid. Med. Cell. Longev. 2016, 3164734 (2016).
    • 15. Ferreira CA, Ni D, Rosenkrans ZT, Cai W. Scavenging of reactive oxygen and nitrogen species with nanomaterials. Nano. Res. 11(10), 4955–4984 (2018).
    • 16. Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S. Cytochrome c release from mitochondria proceeds by a two-step process. Proc. Natl Acad. Sci. USA 99(3), 1259–1263 (2002).
    • 17. Rodríguez-Vargas JM, Ruiz-Magaña MJ, Ruiz-Ruiz C et al. ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Cell Res. 22(7), 1181–1198 (2012).
    • 18. Wang Y, Kim NS, Haince JF et al. Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci. Signal. 4(167), ra20 (2011).
    • 19. Liu J, Qiu Z, Wang S, Zhou L, Zhang S. A modified double-emulsion method for the preparation of daunorubicin-loaded polymeric nanoparticle with enhanced in vitro anti-tumor activity. Biomed. Mater. 5(6), 065002 (2010).
    • 20. Hoa LTM, Chi NT, Nguyen LH, Chien DM. Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method. J. Exp. Nanosci. 7(2), 189–197 (2012).
    • 21. Win KY, Feng SS. In vitro and in vivo studies on vitamin E TPGS-emulsified poly (D, L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation. Biomaterials 27(10), 2285–2291 (2006).
    • 22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193(1), 265–275 (1951). • Protein estimation, required for most of the techniques including gelatin zymography and western blotting, was carried out following the method of Lowry et al.
    • 23. Roy A, Ghosh S, Chakraborty R. Comparative research of anti-inflammatory effects of different dietary antioxidants on alcohol-induced damage in gastric cells. Free Radic. Antioxid. 9(1), 16–21 (2019).
    • 24. Ministry of Environment, Forest and Climate Change (MoEF&CC), Govt. of India. Compendium of CPCSEA (2018). https://cpcsea.nic.in/WriteReadData/userfiles/file/Compendium%20of%20CPCSEA.pdf
    • 25. Organisation for Economic Cooperation and Development (OECD). Guideline for Testing of Chemicals No. 423. Acute Oral Toxicity – Acute Toxic Class Method (2001). • The universally accepted guideline for testing acute oral toxicity in rodents for any chemicals.
    • 26. Ghosh S, Dungdung SR, Chowdhury ST et al. Encapsulation of the flavonoid quercetin with an arsenic chelator into nanocapsules enables the simultaneous delivery of hydrophobic and hydrophilic drugs with a synergistic effect against chronic arsenic accumulation and oxidative stress. Free Radic. Biol. Med. 51(10), 1893–1902 (2011). • Forms the basis of this study that nanoencapsuled natural products delivers the drug to target cells with a much faster rate than that of free components.
    • 27. Elingold I, Isollabella MP, Casanova MB et al. Mitochondrial toxicity and antioxidant activity of a prenylated flavonoid isolated from Dalea elegans. Chem. Biol. Interact. 171(3), 294–305 (2008).
    • 28. Recknagel RO, Glende EA Jr. Spectrophotometric detection of lipid conjugated dienes. Methods Enzymol. 105, 331–337 (1984).
    • 29. Davila JC, Davis PJ, Acosta D. Changes in glutathione and cellular energy as potential mechanisms of papaverine-induced hepatotoxicity in vitro. Toxicol. Appl. Pharmacol. 108(1), 28–36 (1991).
    • 30. Pulli B, Ali M, Forghani R et al. Measuring myeloperoxidase activity in biological samples. PLOS ONE 8(7), e67976 (2013).
    • 31. Dikalov SI, Harrison DG. Methods for detection of mitochondrial and cellular reactive oxygen species. Antioxid. Redox. Signal. 20(2), 372–382 (2014).
    • 32. Naseer M, Ullah I, Narasimhan M et al. Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain. Cell Death Dis. 5, e1150 (2014).
    • 33. Ghosh S, Roy A, Singhania A et al. In-vivo and in-vitro toxicity test of molecularly engineered PCMS: a potential drug for wireless remote controlled treatment. Toxicol. Rep. 5, 1044–1052 (2018).
    • 34. Mazumder S, De R, Debsharma S et al. Indomethacin impairs mitochondrial dynamics by activating the PKCζ-p38-DRP1 pathway and inducing apoptosis in gastric cancer and normal mucosal cells. J. Biol. Chem. 294(20), 8238–8258 (2019).
    • 35. Basak M, Mahata T, Chakraborti S et al. Malabaricone C attenuates nonsteroidal anti-inflammatory drug-induced gastric ulceration by decreasing oxidative/nitrative stress and inflammation and promoting angiogenic autohealing. Antioxid. Redox. Signal. 32(11), 766–784 (2020).
    • 36. Wang Y, Chen Y, Zhang X, Lu Y, Chen H. New insights in intestinal oxidative stress damage and the health intervention effects of nutrients: a review. J. Functional Foods 75, 104248 (2020).
    • 37. Gardner J, Ghorpade A. Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix metalloproteinases in the central nervous system. J. Neurosci. Res. 74(6), 801–806 (2003).
    • 38. Webster KA. Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species. Future Cardiol. 8(6), 863–884 (2012).
    • 39. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J. Clin. Biochem. Nutr. 48(2), 107–111 (2011). •• Illustrates the basis of choosing NSAID-mediated-induced gastric ulcer model.
    • 40. Bank A, Yu J, Zhang L. NSAIDs downregulate Bcl-X(L) and dissociate BAX and Bcl-X(L) to induce apoptosis in colon cancer cells. Nutr. Cancer 60, 98–103 (2008).
    • 41. Kinnally KW, Peixoto PM, Ryu SY, Dejean LM. Is mPTP the gatekeeper for necrosis, apoptosis, or both? Biochim. Biophys. Acta 1813(4), 616–622 (2011).
    • 42. Shamas-Din A, Kale J, Leber B, Andrews DW. Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb. Perspect. Biol. 5(4), a008714 (2013).