Polymeric nanoparticles loaded naringin and naringenin: effect of solvent, characterization, photodegradation and stability studies

Leticia Malgarim Cordenonsi; Rafaela Martins Sponchiado; Jardel Rodrigo Bandeira; Roberto Chris Vianna Santos; Renata Platchek Raffin; Elfrides Eva Scherman Schapoval

doi:10.22456/2527-2616.108783

Authors

Leticia Malgarim Cordenonsi Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Rafaela Martins Sponchiado Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Jardel Rodrigo Bandeira Programa de Pós-Graduação em Nanociências - Universidade Franciscana
Roberto Chris Vianna Santos Microbiology and Parasitology Department - Federal University of Santa Maria
Renata Platchek Raffin Programa de Pós-Graduação em Nanociências - Universidade Franciscana
Elfrides Eva Scherman Schapoval Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul

DOI:

https://doi.org/10.22456/2527-2616.108783

Keywords:

Flavonoids, Naringin, Naringenin, Nanoparticles, Stability

Abstract

Naringin (NAR) and naringenin (NGE) are flavonoids with important effects, such as antioxidant, nephroprotective and anti-inflammatory action. However, factors such as poor solubility and oral bioavailability, gastrointestinal instability and extensive first pass metabolism lead to limited deliverability. As far as we know, there are no papers describing the use of combination of NAR and NGE in nanoparticles. This paper describes the development and characterization of new nanoparticles containing NAR and NGE (NAR-NGE-NPs) which were prepared by nanoprecipitation using ethanol or mixture of solvents. Size distribution of NAR-NGE-NPs demonstrated a narrow distribution (121 nm), low polydispersity (< 0.1), and encapsulation efficiencies were greater than 80%. Infrared spectroscopy analyses confirmed the structure of NAR-NGE-NPs and in transmission electron microscopy, NAR-NGE-NPs presented a spherical and regular shape. A degradation study by UV-C, NAR-NGE-NPs improved photostability and conferred protection against NAR and NGE degradation. Minimal inhibitory concentrations of NAR and NGE were evaluated, however samples did not show antimicrobial activity. In this investigation, new NAR-NGE-NPs were successfully developed by a nanoprecipitation technique, using Endragit®L100 as polymer and ethanol as solvent.

Downloads

Download data is not yet available.

References

Sayre CL, Gerde KD, Yáñez JA, Davies NM. Clinical Pharmacokinetics of Flavonoids. In Flavonoid Pharmacokinetics: Methods of Analysis, Preclinical and Clinical Pharmacokinetics, Safety and Toxicology, 1st Eds.; John Wiley & Sons, Inc. Hoboken., USA, 2012; pp. 195-247.

Badarya OA, Abdel-Maksoudb S, Ahmedd WA, Owieda GH. Naringenin attenuates cisplatin nephrotoxicity in rats. Life Sciences 2005, 76, 2125–35.

Ghasemzadeh A, Jaafar HZ, Rahmat A. Antioxidant Activities, Total Phenolics and Flavonoids Content in Two Varieties of Malaysia Young Ginger (Zingiber officinale Roscoe). Molecules 2010, 15, 4324-33.

Liu Q, Lu L, Xião M. Cell surface engineering of a-Lrhamnosidase for naringin hydrolysis. Bioresour Technol 2012, 123, 144–49.

Kandhare AD, Raygude KS, Ghosh PA, Ghule E, Bodhankar SL. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia 2012, 83, 650–59.

Choi JS, Yokozawa T, Oura H. Improvement of hyperglycemia and hyperlipemia in streptozotocindiabetic rats by a methanolic extract of Prunus davidiana stems and its main component, pruning. Planta Med 1991, 57, 208–11.

Mulvihill EE, Assini JM, Sutherland BG, DiMattia A, Khami M, Koppes JB, Sawyez CG, Whitman SC, Huff MW. Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fatfed low-density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol 2010, 30, 742–48.

Lee SM, Lee JH, Bae YC. Swelling behaviors of poly (methyl methacrylate) nano-sized gels in PEG/alcohol solutions. Fluid Phase Equilib 2014, 382, 107-15.

Semalty A, Semalty M, Singh D, Rawat MSM. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Inclusion Phenom Macrocyclic Chem 2010, 67, 253– 60.

Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther 1996, 60, 34–40.

Munin A, Edwards-Lévy F. Encapsulation of Natural Polyphenolic Compounds, a Review. Pharmaceutics 2011, 3, 793-829.

Vauthier C, Bouchemal K. Methods for the Preparation and Manufacture of Polymeric Nanoparticles. Pharm Res 2009, 26,1025-58.

Nollenberger K. Poly (meth) acrylate-based coatings. Int J Pharm 2013, 457, 461-69.

Fessi HPFD, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 1989, 22, R1-4.

Cordenonsi LM; Bromberger NG, Raffin RP, Scherman EE. Simultaneous separation and sensitive detection of naringin and naringenin in nanoparticles by chromatographic method indicating stability and photodegradation kinetics. Biomed Chromatogr 2016, 30, 155-162.

Nudelman NS. Estabilidad de medicamentos, 1st ed., Buenos Aires: El Atheneo, 1975.

Carstensen JT, Rhodes CT. Drug Stability: Principles and Practices, 3rd ed., Nova York: Marcel Dekker, 2000.

CLSI - Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 6th ed., Wayne: Approved Standard, 2008.

Birnbaum DT, Kosmala JD, Henthorn DB, BrannonPeppas L. Controlled release of β-estradiol from PLAGA microparticles: The effect of organic phase solvent on encapsulation and release. J. Controlled Release 2000, 65, 375-87.

Peltonen L, Koistinen P, Karjalainen M, Häkkinen A, Hirvonen J. The effect of cosolvents on the formulation of nanoparticles from low-molecular-weight poly (I) lactide. AAPS Pharm Sci Tech 2002, 3. 52-8.

Song KC, Lee HS, Choung IY, Cho KI, Ahn Y, Choi EJ. The effect of type of organic phase solvents on the particle size of poly (d, l-lactide-co-glycolide) nanoparticles. Colloids Surf A 2006, 276, 162-67.

Camili ST, Buyukserin F, Balci O, Budak GG. Size controlled synthesis of sub-100 nm monodisperse poly(methylmethacrylate) nanoparticles using surfactant-free emulsion polymerization. J. Colloid Interface Sci 2010, 344. 528-32.

Haznedar S, Dortunc B. Preparation and in vitro evaluation of Eudragit microspheres containing acetazolamide. Int J Pharm 2004, 269,131-40.

Hoffart V, Ubrich N, Simonin C, Babak V, Vigneron C, Hoffman M, Lecompte T, Maincent P. Low molecular weight heparinloaded polymeric nanoparticles: formulation, characterisation, and release characteristics. Drug Dev Ind Pharm 2002, 28, 1091-99.

Galindo-Rodrigues S, Allémann E, Fessi H, Doelker E. Physicochemical Parameters Associated with Nanoparticle Formation in the Salting-out, Emulsification-Diffusion and Nanoprecipitation Methods. Pharm Res 2004, 21, 1428-39.

Couvreur P, Barratt G, Fattal E, Legrand P, Vauthier C. Nanocapsule technology: a review. Crit Rev Ther Drug Carrier Syst 2002, 19, 99-134.

Moghimi SM, Hunter AC, Murray JC. Longcirculating and target-specific nanoparticles: theory to practice. Pharmacol Rev 2001, 53, 283-318.

Williams DB, Carter CB. The Transmission Electron Microscope, 1st ed., USA: Springer, 1996.

Pavia DL, Lampman GM, Kriz GS. Introduction to Spectroscopy: a guide for students of organic chemistry, 3 th ed., South Melbourme: Brooks/Cole, 2001.

Yu L. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv Drug Delivery Rev 2001, 48, 27-42.

Lauro MR, Simone F, Sansone F, Iannelli P, Aquino RP. Preparations and release characteristics of naringin and naringenin gastro-resistant microparticles by spray-drying. J. Drug Delivery Sci Technol 2007, 17, 119-24.

Sansone F, Picerno P, Mencherini T, Villecco F, D’ursi AM, Aquino RP, Lauro MR. Flavonoid microparticles by spray-drying: Influence of enhancers of the dissolution rate on properties and stability. J Food Eng 2001, 103, 188-96.

Yang L, Ma S, Zhou S, Chen W, Yuan M, Yin Y, Yang X. Preparation and characterization of inclusion complexes of naringenin with b-cyclodextrin or its derivative. Carbohydr Polym 2013, 98, 861-69.

Malesuik MD, Gonçalves HML, Paim CS, Schapoval EES, Steppe M. LC: analysis of photodegradation kinetics of nitazoxanide in pharmaceutical formulations. J Chromatogr Sci 2009, 47, 745-48.

Hsu CH, Cui Z, Mumper RJ, Jay M. Preparation and characterization of coenzyme Q10-loaded PMMA nanoparticles by a new emulsification process based on microfluidization. Colloids Surf A. 2003, 4, 24-35.

Mora-Huertas CE, Fessi H, Elaissari A. Polymerbased nanocapsules for drug delivery. Int J Pharm 2010, 385, 113–42.

Pohlmann AR, Weiss V, Mertins O, da Silveira NP, Guterres SS. Spray-dried indomethacin-loaded polyester nanocapsules and nanospheres: development, stability evaluation and nanostructure models. Eur J Pharm Sci 2002, 16, 305-12.

Lepeltier E, Bourgaux C, Couvreur P. Nanoprecipitation and the “Ouzo effect”: Application to drug delivery devices. Adv Drug Delivery Rev 2014, 71, 86-97.

Zhu Z. Flash Nanoprecipitation: Prediction and Enhancement of Particle Stability via Drug Structure. Mol Pharmaceutics 2014, 11, 776-86.

Céliz G, Daz M, Audisi MC. Antibacterial activity of naringin derivatives against pathogenic strains. J Appl Microbiol 2011, 111, 731-38.

Vandeputte OM, Kiendrebeogo M, Rasamiravaka T, Stevigny C, Duez P, Rajaonson S, Diallo B, Mol A, Baucher M, Jaziri ME. The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1. Microbiology 2011, 157, 2120-32.