Preparation of stable enteric folic acid-loaded microfiber using the electrospinning method

Document Type : Original Article

Authors

1 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

6 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Folic acid is an essential vitamin, labile to hydrolysis in the acidic environment of the stomach with low water solubility and bioavailability. In order to solve these problems, enteric oral folic acid-loaded microfibers with a pH-sensitive polymer by electrospinning method were prepared.
Materials and Methods: Electrospinning was performed at different folic acid ratios and voltages. Fibers were evaluated in terms of mechanical strength, acidic resistance, and drug release. Additionally, DSC (Differential Scanning Calorimetry), FTIR (Fourier-transform infrared spectroscopy), and XRD (X-ray diffraction) analyses were performed on the optimal formulation. 
Results: Drug ratio and voltage had a considerable effect on fibers’ entrapment efficiency, acid resistance, and mechanical strength. Based on the obtained results, the optimum formulation containing 1.25% of the drug/polymer was prepared at 18 kV. The entrapment efficiency of the optimal sample was above 90% with an acid resistance of higher than 70%. The tensile test confirmed the high mechanical properties of the optimum microfiber. DSC and XRD tests indicated that folic acid was converted to an amorphous form in the fiber structure and the FTIR test confirmed the formation of a chemical bond between the drug and the polymer. The release of the drug from the optimal fiber was about 90% in 60 min.
Conclusion: In conclusion, the optimal formulation of folic acid with proper mechanical properties can be used as a candidate dosage form for further bioavailability investigations.

Keywords

References

1. Wang XQ, Zhang Q. PH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs. Eur J Pharm Biopharm 2012; 82:219-229. 
2. Gao W, Chan JM, Farokhzad OC. pH-responsive nanoparticles for drug delivery. Sci Exch 2009; 2:249–249. 
3. Nasef AM, Gardouh AR, Ghorab MM. Formulation and in-vitro evaluation of pantoprazole loaded pH-sensitive polymeric nanoparticles. Futur J Pharm Sci 2017; 3:103–117. 
4. Li B, He J, Evans DG, Duan X. Enteric-coated layered double hydroxides as a controlled release drug delivery system. Int J Pharm 2004; 287:89–95. 
5. Raffin RP, Colomé LM, Pohlmann AR, Guterres SS. Preparation, characterization, and in vivo anti-ulcer evaluation of pantoprazole-loaded microparticles. Eur J Pharm Biopharm 2006; 63:198–204. 
6. Yoo JW, Giri N, Lee CH. PH-sensitive Eudragit nanoparticles for mucosal drug delivery. Int J Pharm 2011; 403:262–267. 
7. Barbosa J de AB, de França CA, Gouveia JJ de S, Gouveia G V., da Costa MM, de Oliveira HP. Eudragit E100/poly(ethylene oxide) electrospun fibers for DNA removal from aqueous solution. J Appl Polym Sci 2019; 136:47479. 
8. Ofridam F, Lebaz N, Gagnière É, Mangin D, Elaissari A. Polymethylmethacrylate derivatives Eudragit E100 and L100: Interactions and complexation with surfactants. Polym Adv Technol 2021; 32:379–390. 
9. Karthikeyan K, Guhathakarta S, Rajaram R, Korrapati PS. Electrospun zein/eudragit nanofibers based dual drug delivery system for the simultaneous delivery of aceclofenac and pantoprazole. Int J Pharm 2012; 438:117–122. 
10. Turanlı Y, Tort S, Acartürk F. Development and characterization of methylprednisolone loaded delayed release nanofibers. J Drug Deliv Sci Technol 2019; 49:58–65. 
11. Ding Y, Dou C, Chang S, Xie Z, Yu DG, Liu Y, et al. Core-shell eudragit S100 nanofibers preparedvia triaxial electrospinning to providea colon-targeted extended drug release. Polymers (Basel) 2020; 12:2034. 
12. Di Tinno A, Cancelliere R, Micheli L. Determination of folic acid using biosensors-a short review of recent progress. Sensors 2021; 21:3360. 
13. Milman N. Intestinal absorption of folic acid - new physiologic & molecular aspects. Indian J Med Res 2012; 136:725–728. 
14. Zhang Y, Xu M-Y, Jiang T-K, Huang W-Z, Wu J-Y. Low generational polyamidoamine dendrimers to enhance the solubility of folic acid: A “dendritic effect” investigation. Chinese Chem Lett 2014; 25:815-818. 
15. Younis IR, Stamatakis MK, Callery PS, Meyer-Stout PJ. Influence of pH on the dissolution of folic acid supplements. Int J Pharm 2009; 367:97–102. 
16. Camacho DH, Uy SJY, Cabrera MJF, Lobregas MOS, Fajardo TJMC. Encapsulation of folic acid in copper-alginate hydrogels and it’s slow in vitro release in physiological pH condition. Food Res Int 2019; 119:15–22. 
17. Ruiz-Rico M, Daubenschüz H, Pérez-Esteve É, Barat JM, Martínez-Mañez R. Enhanced stability of folic acid by encapsulation in phresponsive gated mesoporous silica particles. Proc World Congr New Technol 2015; 202:124–132. 
18. Morie A, Garg T, Goyal AK, Rath G. Nanofibers as novel drug carrier - An overview. Artif Cells, Nanomedicine Biotechnol 2016; 44:135–143. 
19. Potrč T, Baumgartner S, Roškar R, Planinšek O, Lavrič Z, Kristl J, et al. Electrospun polycaprolactone nanofibers as a potential oromucosal delivery system for poorly water-soluble drugs. Eur J Pharm Sci 2015; 75:101–113. 
20. Akhgari A, Heshmati Z, Afrasiabi Garekani H, Sadeghi F, Sabbagh A, Sharif Makhmalzadeh B, et al. Indomethacin electrospun nanofibers for colonic drug delivery: In vitro dissolution studies. Colloids Surfaces B Biointerfaces 2017; 152:29–35. 
21. Mohammadzadehmoghadam S, Dong Y, Davies IJ. Modeling electrospun nanofibers: An overview from theoretical, empirical, and numerical approaches. Int J Polym Mater Polym Biomater 2016; 65:901–915. 
22. Hu X, Liu S, Zhou G, Huang Y, Xie Z, Jing X. Electrospinning of polymeric nanofibers for drug delivery applications. J Control Release 2014; 185:12–21. 
23. Teilaghi S, Movaffagh J, Bayat Z. Preparation as well as evaluation of the nanofiber membrane loaded with Nigella sativa extract using the electrospinning method. J Polym Environ 2020; 28:1614–1625. 
24. He J, Cheng Y, Li P, Zhang Y, Zhang H, Cui S. Preparation and characterization of biomimetic tussah silk fibroin/chitosan composite nanofibers. Iran Polym J (English Ed) 2013; 22:537–547. 
25. Pillay V, Dott C, Choonara YE, Tyagi C, Tomar L, Kumar P, et al. A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. J Nanomater 2013; 2013:1-22. 
26. Abrigo M, McArthur SL, Kingshott P. Electrospun nanofibers as dressings for chronic wound care: Advances, challenges, and future prospects. Macromol Biosci 2014; 14:772–792. 
27. Lasprilla-Botero J, Álvarez-Láinez M, Lagaron JM. The influence of electrospinning parameters and solvent selection on the morphology and diameter of polyimide nanofibers. Mater Today Commun 2018; 14:1–9. 
28. Parin FN, Aydemir Ç. I, Taner G, Yildirim K. Co-electrospun-electrosprayed PVA/folic acid nanofibers for transdermal drug delivery: Preparation, characterization, and in vitro cytocompatibility. J Ind Text 2021;1528083721997185. 
29. Oliveira FM, Segatelli MG, Tarley CRT. Preparation of a new restricted access molecularly imprinted hybrid adsorbent for the extraction of folic acid from milk powder samples. Anal Methods 2016; 8:656–665. 
30. Kim Y, Park EJ, Kim TW, Na DH. Recent progress in drug release testing methods of biopolymeric particulate system. Pharmaceutics 2021; 13:1313. 
31. Abbaspour M, Iraji P, Mahmoudi Z, Rahiman N, Akhgari A. Design and physico-mechanical evaluation of fast-dissolving valsartan polymeric drug delivery system by electrospinning method. Iran J Basic Med Sci 2021; 24: 1683-1694. 
32. Reda RI, Wen MM, El-Kamel AH. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis. Int J Nanomedicine 2017; 12:2335–2351. 
33. Uyar T, Besenbacher F. Electrospinning of uniform polystyrene fibers: The effect of solvent conductivity. Polymer (Guildf) 2008; 49:5336–5343. 
34. Zamani M, Morshed M, Varshosaz J, Jannesari M. Controlled release of metronidazole benzoate from poly ε-caprolactone electrospun nanofibers for periodontal diseases. Eur J Pharm Biopharm 2010; 75:179–185. 
35. Wang M, Wang L, Huang Y. Electrospun hydroxypropyl methyl cellulose phthalate (HPMCP)/erythromycin fibers for targeted release in intestine. J Appl Polym Sci 2007; 106:2177–2184. 
36. ElMessiry M, Fadel N. The tensile properties of electrospun poly vinyl chloride and cellulose acetate (PVC/CA) bi-component polymers nanofibers. Alexandria Eng J 2019; 58:885–890. 
37. Centkowska K, Ławrecka E, Sznitowska M. Technology of orodispersible polymer films with micronized loratadine-influence of different drug loadings on film properties. Pharmaceutics 2020; 12:250. 
38. Bueno JNN, Corradini E, de Souza PR, Marques V de S, Radovanovic E, Muniz EC. Films based on mixtures of zein, chitosan, and PVA: Development with perspectives for food packaging application. Polym Test 2021; 101:107279. 
39. Lim H, Hoag SW. Plasticizer effects on physical-mechanical properties of solvent cast Soluplus® films. AAPS PharmSciTech 2013; 14:903–910. 
40. Lee Y, Kim K, Kim M, Choi DH, Jeong SH. Orally disintegrating films focusing on formulation, manufacturing process, and characterization. J Pharm Investig 2017; 47:183–201. 
41. Charernsriwilaiwat N, Rojanarata T, Ngawhirunpat T, Opanasopit P. Electrospun chitosan/polyvinyl alcohol nanofibre mats for wound healing. Int Wound J 2014; 11:215–222. 
42. Le QP, Uspenskaya M V., Olekhnovich RO, Baranov MA. The mechanical properties of PVC nanofiber mats obtained by electrospinning. Fibers 2021; 9:1–12. 
43. Hrib J, Sirc J, Hobzova R, Hampejsova Z, Bosakova Z, Munzarova M, et al. Nanofibers for drug delivery - Incorporation and release of model molecules, influence of molecular weight and polymer structure. Beilstein J Nanotechnol 2015; 6:1939–1645. 
44. Sancin P, Caputo O, Cavallari C, Passerini N, Rodriguez L, Cini M, et al. Effects of ultrasound-assisted compaction on Ketoprofen/Eudragit®S100 Mixtures. Eur J Pharm Sci 1999; 7:207–213. 
45. Mehta R, Chawla A, Sharma P, Pawar P. Formulation and in vitro evaluation of Eudragit S-100 coated naproxen matrix tablets for colon-targeted drug delivery system. J Adv Pharm Technol Res 2013; 4:31–41. 
46. Burgess K, Li H, Abo-Zeid Y, Fatimah, Williams GR. The effect of molecular properties on active ingredient release from electrospun eudragit fibers. Pharmaceutics 2018; 10:103. 
47. Raffin RP, Colomé LM, Guterres SS, Pohlmann AR. Enteric controlled-release pantoprazole-loaded microparticles prepared by using eudragit S100 and poly(ε-caprolactone) blend. Pharm Dev Technol 2007; 12:463–471. 
48. Ghorab DM, Amin MM, Khowessah OM, Tadros MI. Colon-targeted celecoxib-loaded Eudragit ® S100-coated poly-ε-caprolactone microparticles: Preparation, characterization and in vivo evaluation in rats. Drug Deliv 2011; 18:523–535. 
49. Gazzali AM, Lobry M, Colombeau L, Acherar S, Azaïs H, Mordon S, et al. Stability of folic acid under several parameters. Eur J Pharm Sci 2016; 93:419–430. 
50. Pérez-Masiá R, López-Nicolás R, Periago MJ, Ros G, Lagaron JM, López-Rubio A. Encapsulation of folic acid in food hydrocolloids through nanospray drying and electrospraying for nutraceutical applications. Food Chem 2015; 168:124–133. 
51. Venkatasubbu GD, Ramasamy S, Avadhani GS, Ramakrishnan V, Kumar J. Surface modification and paclitaxel drug delivery of folic acid modified polyethylene glycol functionalized hydroxyapatite nanoparticles. Powder Technol 2013; 235:437–442. 
52. Dutta S, Ganguly BN. Characterization of ZnO nanoparticles grown in presence of folic acid template. J Nanobiotechnology 2012; 10:29. 
53. Hadi MA, Raghavendra Rao NG, Srinivasa Rao A. Formulation and evaluation of pH-responsive mini-tablets for ileo-colonic targeted drug delivery. Trop J Pharm Res 2014; 13:1021–1029. 
54. Ahuja M, Dhake AS, Sharma SK, Majumdar DK. Diclofenac-loaded Eudragit S100 nanosuspension for ophthalmic delivery. J Microencapsul 2011; 28:37–45. 
55. Bashi AM, Haddawi SM, Mezaal MA. Layered double hydroxides nanohybrid intercalation with folic acid used as delivery system and their controlled release properties. Arab J Sci Eng 2013; 38:1663–1680. 
56. Trivedi D. Evaluation of the physicochemical and thermal properties of folic acid: Influence of the energy of consciousness healing treatment. Sch J Food Nutr 2019; 1:142–149. 
57. Chawla A, Sharma P, Pawar P. Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: Formulation, optimization and in vitro evaluation. Acta Pharm 2012; 62:529-545. 
Iranian Journal of Basic Medical Sciences
Volume 25, Issue 3
March 2022
Pages 405-413

Files

Share

How to cite

Statistics