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Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles

Year 2019, Volume: 23 Issue: 5, 914 - 926, 27.06.2025

Abstract

S-adenosyl-L-methionine (SAMe) is an endogenic methyl donor naturally present in all living cells; it has high water solubility, but its bioavailability is low in oral administration due to the first pass effect in the liver. The aim of this study is to prepare colon targeted chitosan nanoparticles containing SAMe by ionic gelation. In the preparation of the formulations, the effects of chitosan concentration, tripolyphosphate (TPP) concentration and the amount of SAMe on the specifications of the nanoparticles such as particle size, zeta potential, encapsulation efficiency, and process yield, were investigated. Drug-excipient interactions were evaluated by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The obtained nanoparticles showed bimodal particle size distribution ranging between 228.3-763.9 nm and their zeta potentials were within 14.10-23.30 mV. The drug encapsulation efficiencies and process yields of the nanoparticles were low. However, when the effects of the process parameters on the characteristics of nanoparticles were examined, the chitosan concentration and SAMe amount were significant parameters affecting particle size. The chitosan concentration was also found to have a significant effect on process yield (p <0.05). Drug release from nanoparticles was evaluated according to different kinetic models and it was found that the release mechanism was Fickian diffusion.

References

  • [1] Birrenbach G, Speiser PP. Polymerized micelles and their use as adjuvants in immunology. J Pharm Sci. 1976; 65: 1763-1766. [CrossRef]
  • [2] des Rieux A, Fievez V, Garinot M, Schneider YJ, Preat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006; 116(1): 1-27. [CrossRef]
  • [3] Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomed. 2016. [CrossRef]
  • [4] Zhao Y, Wang Y, Ran F, Cui Y, Liu C, Zhao Q, et al. A comparison between sphere and rod nanoparticles regarding their in vivo biological behavior and pharmacokinetics. Sci Rep. 2017; 7(1): 1-11. [CrossRef]
  • [5] Lamprecht A, Schäfer U, Lehr CM. Size-Dependent Bioadhesion of Micro- and Nanoparticulate Carriers to the Inflamed Colonic Mucosa. Pharm Res. 2001; 18(6): 788-793. [CrossRef]
  • [6] Pan Y, Li Y, Zhao H, Zheng J, Xu H, Wei G, et al. Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int J Pharm. 2002; 249(139): 139-147. [CrossRef]
  • [7] Patel D, Naik S, Misra A. Improved transnasal transport and brain uptake of tizanidine HCl-loaded thiolated chitosan nanoparticles for alleviation of pain. J Pharm Sci. 2012; 101(2): 690-706. [CrossRef]
  • [8] Li Z, Jiang H, Xu C, Gu L. A review: Using nanoparticles to enhance absorption and bioavailability of phenolic phytochemicals. Food Hydrocoll. 2015; 43: 153-164. [CrossRef]
  • [9] Iglesias N, Galbis E, Díaz-Blanco MJ, Lucas R, Benito E, de-Paz MV. Nanostructured chitosan-based biomaterials for sustained and colon-specific resveratrol release. Int J Mol Sci. 2019; 20, 398. [CrossRef]
  • [10] Rampino A, Borgogna M, Blasi P, Bellich B, Cesaro A. Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm. 2013; 455(1-2): 219-228. [CrossRef]
  • [11] Barbari GR, Dorkoosh FA, Amini M, Sharifzadeh M, Atyabi F, Balalaie S, et al. A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides. Int J Nanomed. 2017; 12: 3471-3483. [CrossRef]
  • [12] Prego C, Torres D, Alonso MJ. The potential of chitosan for the oral administration of peptides. Expert Opin Drug Deliv. 2005; 2(5): 843-854. [CrossRef]
  • [13] Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002; 76: 1151-1157. [CrossRef]
  • [14] Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction. Am J Clin Nutr. 2002; 76: 1148-1150. [CrossRef]
  • [15] The Norwegian Scientific Committee for Food and Environmen, Risk assessment of histidine, methionine, Sadenosylmethionine and tryptophan, 2013.
  • [16] https://vkm.no/download/18.175083d415c86c573b59c3a7/1501675375589/ba7a85274a.pdf (accessed July 25, 2019).
  • [17] Magesh B, Naidu PY, Rajarajeswari GR. S-adenosyl-l-methionine (SAMe)-loaded nanochitosan particles: synthesis, characterisation and in vitro drug release studies. J Exp Nanosci. 2015; 10(11): 828-843. [CrossRef]
  • [18] Food And Drug Administration, Reviewer guidance validation of chromatographic methods, November/1994.
  • [19] https://www.fda.gov/media/75643/download (accessed July 25, 2019).
  • [20] Ozkan Y, Tas C, Ozkan CK, Bayrak Z, Esim O, Ozkan S. İlaçların analiz ve kalite kontrollerinde kullanılan analitik yöntemlerin geçerliliği (validasyon), Gülhane Askeri Tıp Akademisi, Ankara, Türkiye, 2011.
  • [21] Food And Drug Administration, Appendix 1 – ORA validation and verification guidance for human drug analytical methods.
  • [22] https://www.fda.gov/media/82998/download (accessed July 25,2019).
  • [23] Shu XZ, Zhu KJ. The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release. Eur J Pharm Biopharm. 2002; 54: 235-243. [CrossRef]
  • [24] Fan W, Yan W, Xu Z, Ni H. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B Biointerfaces. 2012; 90: 21-27. [CrossRef]
  • [25] Janes KA, Fresneau MP, Marazuela A, Fabra A, Alonso MJ. Chitosan nanoparticles as delivery systems for doxorubicin. J Control Release. 2001; 73: 255-267. [CrossRef]
  • [26] Omar Zaki SS, Ibrahim MN, Katas H. Particle size affects concentration-dependent cytotoxicity of chitosan nanoparticles towards mouse hematopoietic stem cells. J Nanotechnoly. 2015; 2015: 1-5. [CrossRef]
  • [27] Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-In program for modeling and comparison of drug dissolution profiles. AAPS J. 2010; 12(3): 263-271. [CrossRef]
  • [28] Öztürk AA, Güven UA. Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. J Res Pharm. 2019; 23(3): 426-440. [CrossRef]
  • [29] Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2001; 48: 139-157. [CrossRef]
  • [30] Moore JW, Flanner HH. Mathematical comparison of curves with an emphasis on in vitro dissolution profiles. Pharm Technol. 1996; 20: 64-74.
  • [31] Qi L, Xu Z, Jiang X, Hu C, Zou X. Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr Res. 2004; 339(16): 2693-2700. [CrossRef]
  • [32] Dhawade PP, Jagtap RN. Characterization of the glass transition temperature of chitosan and its oligomers by temperature modulated differential scanning calorimetry. Adv Appl Sci Res. 2012; 3(3): 1372-1382.
  • [33] Neufeld L, Bianco-Peled H. Pectin–chitosan physical hydrogels as potential drug delivery vehicles. Int J Biol Macromol. 2017; 101: 852-861. [CrossRef]
  • [34] Calvo P, Remunan lopez C, Vila-Jato JL, Alonso MJ. Novel hydrophilic chitosan–polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci. 1997; 63(1): 125-132. [CrossRef]
  • [35] Bou-Chacra N, Curo Melo KJ, Morales IAC, Stippler ES, Kesisoglou F, Yazdanian M, et al. Evolution of choice of solubility and dissolution media after two decades of biopharmaceutical classification system. AAPS J. 2017; 19(4): 989-1001. [CrossRef]
  • [36] Yüksel N, Beba L. Preparation and optimization of superabsorbent hydrogel micromatrices based on poly(acrylic acid), partly sodium salt-g-poly(ethylene oxide) for modified release of indomethacin Drug Dev Ind Pharm. 2009; 35(6): 756-767. [CrossRef]
  • [37] Surya Teja SP, Damodharan N. 23 full factorial model for particle size optimization of methotrexate loaded chitosan nanocarriers: a design of experiments (DoE) approach. Biomed Res Int. 2018; Article ID 7834159. [CrossRef]
There are 37 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Biotechnology, Pharmaceutical Delivery Technologies
Journal Section Articles
Authors

Ahmet Doğan Ergin This is me

Zerrin Sezgin Bayındır

Nilüfer Yüksel This is me

Publication Date June 27, 2025
Published in Issue Year 2019 Volume: 23 Issue: 5

Cite

APA Ergin, A. D., Sezgin Bayındır, Z., & Yüksel, N. (2025). Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles. Journal of Research in Pharmacy, 23(5), 914-926.
AMA Ergin AD, Sezgin Bayındır Z, Yüksel N. Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles. J. Res. Pharm. July 2025;23(5):914-926.
Chicago Ergin, Ahmet Doğan, Zerrin Sezgin Bayındır, and Nilüfer Yüksel. “Characterization and Optimization of Colon Targeted S-Adenosyl-L-Methionine Loaded Chitosan Nanoparticles”. Journal of Research in Pharmacy 23, no. 5 (July 2025): 914-26.
EndNote Ergin AD, Sezgin Bayındır Z, Yüksel N (July 1, 2025) Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles. Journal of Research in Pharmacy 23 5 914–926.
IEEE A. D. Ergin, Z. Sezgin Bayındır, and N. Yüksel, “Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles”, J. Res. Pharm., vol. 23, no. 5, pp. 914–926, 2025.
ISNAD Ergin, Ahmet Doğan et al. “Characterization and Optimization of Colon Targeted S-Adenosyl-L-Methionine Loaded Chitosan Nanoparticles”. Journal of Research in Pharmacy 23/5 (July 2025), 914-926.
JAMA Ergin AD, Sezgin Bayındır Z, Yüksel N. Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles. J. Res. Pharm. 2025;23:914–926.
MLA Ergin, Ahmet Doğan et al. “Characterization and Optimization of Colon Targeted S-Adenosyl-L-Methionine Loaded Chitosan Nanoparticles”. Journal of Research in Pharmacy, vol. 23, no. 5, 2025, pp. 914-26.
Vancouver Ergin AD, Sezgin Bayındır Z, Yüksel N. Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles. J. Res. Pharm. 2025;23(5):914-26.