Generic placeholder image

Current Nutraceuticals

Editor-in-Chief

ISSN (Print): 2665-9786
ISSN (Online): 2665-9794

Research Article

Microscopic Evidence of the Behavior of pH-sensitive Food-grade Polymeric Delivery Systems

Author(s): Salvatore Rizzo, Giuseppe Cosentino, Elide Zingale, Angela Bonaccorso, Salvatore Petralia, Francesca Monforte, Guglielmo G. Condorelli, Claudia Carbone* and Rosario Pignatello*

Volume 4, 2023

Published on: 30 March, 2023

Article ID: e010223213354 Pages: 13

DOI: 10.2174/2665978604666230201144421

Price: $65

Abstract

Background: Colon delivery systems are designed for the oral delivery of active compounds in the large intestine. Food-grade copolymers Eudraguard® Biotic (EUGB) and control (EUGC) have been investigated to develop colloidal systems loading natural active ingredients.

Methods: In this study, we evaluated the degradation process of these matrices in simulated gastric, intestinal and colonic conditions. Microparticles made of EUGB and EUGC, alone or in combination, were loaded with the model compound resveratrol (RSV). A parallel study was performed on in vitro RSV release and SEM analysis of microparticles kept at different pH values.

Results: All systems ensured a limited gastric release of RSV (below 20%), presenting only small pores on the surface of microparticles treated with simulated gastric fluid. EUGB microparticles showed the maximum release in simulated colon fluid (SCF), showing a complete dissolution of the microparticle matrix. The EUGC-based system allowed a prolonged release of RSV over time, and in SCF, it showed only partial degradation. Using mixed EUGB/EUGC matrices, a prolonged RSV release was observed along the intestinal tract.

Conclusion: Overall, EUGB and EUGC copolymers were able to modulate and localize the release of entrapped cargo in the small intestine and colon. They could have interesting applications in treating bowel diseases synergistically with other therapeutic strategies.

[1]
Badhana, S.; Garud, N.; Garud, A. Colon specific drug delivery of mesalamine using eudragit S100-coated chitosan microspheres for the treatment of ulcerative colitis. Int. Curr. Pharm. J., 2013, 2(3), 42-48.
[http://dx.doi.org/10.3329/icpj.v2i3.13577]
[2]
Biondi, M.; Indolfi, L.; Ungaro, F.; Quaglia, F.; La Rotonda, M.I.; Netti, P.A. Bioactivated collagen-based scaffolds embedding protein-releasing biodegradable microspheres: Tuning of protein release kinetics. J. Mater. Sci. Mater. Med., 2009, 20(10), 2117-2128.
[http://dx.doi.org/10.1007/s10856-009-3766-5] [PMID: 19449203]
[3]
Bott, C.; Rudolph, M.W.; Schneider, A.R.J.; Schirrmacher, S.; Skalsky, B.; Petereit, H.U.; Langguth, P.; Dressman, J.B.; Stein, J. In vivo evaluation of a novel pH- and time-based multiunit colonic drug delivery system. Aliment. Pharmacol. Ther., 2004, 20(3), 347-353.
[http://dx.doi.org/10.1111/j.1365-2036.2004.02033.x] [PMID: 15274672]
[4]
Cui, M.; Zhang, M.; Liu, K. Colon-targeted drug delivery of polysaccharide-based nanocarriers for synergistic treatment of inflammatory bowel disease: A review. Carbohydr. Polym., 2021, 272, 118530.
[http://dx.doi.org/10.1016/j.carbpol.2021.118530] [PMID: 34420762]
[5]
Curcio, C.; Bonaccorso, A.; Musumeci, T.; Pignatello, R. Oral controlled delivery of natural compounds using food-grade polymer microparticles. Curr. Nutra., 2021, 2(2), 145-153.
[http://dx.doi.org/10.2174/2665978601999201126212614]
[6]
Curcio, C.; Greco, A.S.; Rizzo, S.; Saitta, L.; Musumeci, T.; Ruozi, B.; Pignatello, R. Development, optimization and characterization of Eudraguard®-based microparticles for colon delivery. Pharmaceuticals, 2020, 13(6), 131.
[http://dx.doi.org/10.3390/ph13060131] [PMID: 32599861]
[7]
de Arce Velasquez, A.; Ferreira, L.M.; Stangarlin, M.F.L.; da Silva, C.B.; Rolim, C.M.B.; Cruz, L. Novel Pullulan-Eudragit® S100 blend microparticles for oral delivery of risedronate: Formulation, in vitro evaluation and tableting of blend microparticles. Mater. Sci. Eng. C, 2014, 38(1), 212-217.
[http://dx.doi.org/10.1016/j.msec.2014.02.003] [PMID: 24656371]
[8]
World Health Organization. Dissolution test for solid dosage forms. Draft proposal for revision in The International Pharmacopoeia. June 2022. Available from: https://cdn.who.int/media/docs/default-source/medicines/norms-and-standards/current-projects/qas20-837-dissolution-test-for-solid-oral-dosage-forms.pdf?sfvrsn=f712c6df_2
[9]
Dvořácková, K.; Kalėdaitė, R.; Gajdziok, J.; Rabišková, M.; Bajerová, M.; Muselík, J.; Lažauskas, R.; Pečiūra, R. The development of Eudragit® NM-based controlled-release matrix tablets. Medicina, 2012, 48(4), 192-202.
[http://dx.doi.org/10.3390/medicina48040028]
[10]
Dubey, R.; Dubey, R.; Omrey, P.; Vyas, S.P.; Jain, S.K. Development and characterization of colon specific drug delivery system bearing 5-ASA and camylofine dihydrochloride for the treatment of ulcerative colitis. J. Drug Target., 2010, 18(8), 589-601.
[http://dx.doi.org/10.3109/10611860903572933] [PMID: 20088681]
[11]
Eisele, J.; Haynes, G.; Kreuzer, K.; Hall, C. Toxicological assessment of anionic methacrylate copolymer: I. Characterization, bioavailability and genotoxicity. Regul. Toxicol. Pharmacol., 2016, 82, 39-47.
[http://dx.doi.org/10.1016/j.yrtph.2016.11.009] [PMID: 27825834]
[12]
Evonik datasheets. Available from: https://healthcare.evonik.com/en/products/nutritional-coatings/ (Accessed on: May 20, 2022).
[13]
Ghattamaneni, N.K.R.; Panchal, S.K.; Brown, L. Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease. Pharmacol. Res., 2018, 132, 99-107.
[http://dx.doi.org/10.1016/j.phrs.2018.04.015] [PMID: 29680446]
[14]
Klein, S. The use of biorelevant dissolution media to forecast the in vivo performance of a drug. AAPS J., 2010, 12(3), 397-406.
[http://dx.doi.org/10.1208/s12248-010-9203-3] [PMID: 20458565]
[15]
Laracuente, M.L.; Yu, M.H.; McHugh, K.J. Zero-order drug delivery: State of the art and future prospects. J. Control. Release, 2020, 327, 834-856.
[http://dx.doi.org/10.1016/j.jconrel.2020.09.020] [PMID: 32931897]
[16]
Lautenschläger, C.; Schmidt, C.; Fischer, D.; Stallmach, A. Drug delivery strategies in the therapy of inflammatory bowel disease. Adv. Drug Deliv. Rev., 2014, 71, 58-76.
[http://dx.doi.org/10.1016/j.addr.2013.10.001] [PMID: 24157534]
[17]
Lee, S.H.; Bajracharya, R.; Min, J.Y.; Han, J.W.; Park, B.J.; Han, H.K. Strategic approaches for colon targeted drug delivery: An overview of recent advancements. Pharmaceutics, 2020, 12(1), 68.
[http://dx.doi.org/10.3390/pharmaceutics12010068] [PMID: 31952340]
[18]
Mathematical models of drug release. In: Strategies to Modify the Drug Release from Pharmaceutical Systems; Elsevier: Amsterdam, 2015; pp. 63-86.
[19]
Meng, T.; Xiao, D.; Muhammed, A.; Deng, J.; Chen, L.; He, J. Anti-inflammatory action and mechanisms of resveratrol. Molecules, 2021, 26(1), 229.
[http://dx.doi.org/10.3390/molecules26010229] [PMID: 33466247]
[20]
Mijan, M.A.; Lim, B.O. Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends. World J. Gastroenterol., 2018, 24(25), 2673-2685.
[http://dx.doi.org/10.3748/wjg.v24.i25.2673] [PMID: 29991873]
[21]
Mircioiu, C.; Voicu, V.; Anuta, V.; Tudose, A.; Celia, C.; Paolino, D.; Fresta, M.; Sandulovici, R.; Mircioiu, I. Mathematical modeling of release kinetics from supramolecular drug delivery systems. Pharmaceutics, 2019, 11(3), 140.
[http://dx.doi.org/10.3390/pharmaceutics11030140] [PMID: 30901930]
[22]
Musumeci, T.; Bonaccorso, A.; Carbone, C.; Impallomeni, G.; Ballistreri, A.; Duskey, J.T.; Puglisi, G.; Pignatello, R. Development and biocompatibility assessments of poly(3-hydroxybutyrate-co-ε-caprolactone) microparticles for diclofenac sodium delivery. J. Drug Deliv. Sci. Technol., 2020, 60, 102081.
[http://dx.doi.org/10.1016/j.jddst.2020.102081]
[23]
Musumeci, T.; Cupri, S.; Bonaccorso, A.; Impallomeni, G.; Ballistreri, A.; Puglisi, G.; Pignatello, R. Technology assessment of new biode-gradable poly(R‐3‐hydroxybutyrate‐co‐1,4‐butylene adipate) copolymers for drug delivery. J. Appl. Polym. Sci., 2019, 136(12), 47233.
[http://dx.doi.org/10.1002/app.47233]
[24]
Nunes, S.; Danesi, F.; Del Rio, D.; Silva, P. Resveratrol and inflammatory bowel disease: the evidence so far. Nutr. Res. Rev., 2018, 31(1), 85-97.
[http://dx.doi.org/10.1017/S095442241700021X] [PMID: 29191255]
[25]
Pignatello, R.; Consoli, P.; Puglisi, G. In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles. J. Microencapsul., 2000, 17(3), 373-383.
[http://dx.doi.org/10.1080/026520400288337] [PMID: 10819424]
[26]
Pignatello, R.; Pecora, T.M.G.; Cutuli, G.G.; Catalfo, A.; De Guidi, G.; Ruozi, B.; Tosi, G.; Cianciolo, S.; Musumeci, T. Antioxidant activity and photostability assessment of trans-resveratrol acrylate microspheres. Pharm. Dev. Technol., 2019, 24(2), 222-234.
[http://dx.doi.org/10.1080/10837450.2018.1455697] [PMID: 29565215]
[27]
Scientific opinion on the safety of anionic methacrylate copolymer for the proposed uses as a food additive. (2010). EFSA J., 1656, 8(7) .
[28]
Shin, D.W.; Lim, B.O. Nutritional interventions using functional foods and nutraceuticals to improve inflammatory bowel disease. J. Med. Food, 2020, 23(11), 1136-1145.
[http://dx.doi.org/10.1089/jmf.2020.4712] [PMID: 33047999]
[29]
Spogli, R.; Bastianini, M.; Ragonese, F.; Iannitti, R.; Monarca, L.; Bastioli, F.; Nakashidze, I.; Brecchia, G.; Menchetti, L.; Codini, M.; Arcuri, C.; Mancinelli, L.; Fioretti, B. Solid dispersion of resveratrol supported on magnesium dihydroxide (Resv@MDH) microparticles improves oral bioavailability. Nutrients, 2018, 10(12), 1925.
[http://dx.doi.org/10.3390/nu10121925] [PMID: 30563110]
[30]
Wang, Q.S.; Wang, G.F.; Zhou, J.; Gao, L.N.; Cui, Y.L. Colon targeted oral drug delivery system based on alginate-chitosan microspheres loaded with icariin in the treatment of ulcerative colitis. Int. J. Pharm., 2016, 515(1-2), 176-185.
[http://dx.doi.org/10.1016/j.ijpharm.2016.10.002] [PMID: 27713029]
[31]
Xun, W.; Fu, Q.; Shi, L.; Cao, T.; Jiang, H.; Ma, Z. Resveratrol protects intestinal integrity, alleviates intestinal inflammation and oxidative stress by modulating AhR/Nrf2 pathways in weaned piglets challenged with diquat. Int. Immunopharmacol., 2021, 99, 107989.
[http://dx.doi.org/10.1016/j.intimp.2021.107989] [PMID: 34303281]
[32]
Zhang, F. Melt-extruded Eudragit® FS-based granules for colonic drug delivery. AAPS Pharm. Sci. Tech., 2016, 17(1), 56-67.
[http://dx.doi.org/10.1208/s12249-015-0357-2] [PMID: 26162974]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy