SYNTHESIS AND CHARACTERIZATION OF POLY D-L LACTIDE (PLA) NANOPARTICLES FOR THE DELIVERY OF QUERCETIN

Authors

  • Bharathi Sambandam Centre for Nanoscience and Technology Anna University Chennai
  • Sathesh Kumar S Department of Pharmaceutics School of Pharmaceutical Sciences VELS University, Chennai.
  • Arivarasan Ayyaswamy Centre for Nanoscience and Technology Anna University Chennai
  • Nagarjuna Yadav B V Department of Pharmaceutics School of Pharmaceutical Sciences VELS University, Chennai.
  • Devasena Thiyagarajan Centre for Nanoscience and Technology Anna University Chennai

Keywords:

Quercetin, Nanoprecipitation, PLA nanoparticles, Antioxidant

Abstract

Objectives: Synthesis and optimization of Poly D-L Lactide (PLA) nanoparticles for the delivery of an antioxidant molecule quercetin.

Methods: The quercetin was encapsulated by PLA nanoparticles by nanoprecipitation method. The average particle size and the electric charge for different formulations were measured by particle size and zeta potential analyzer. The quercetin loaded PLA nanoparticles (Q-PLAN) was characterized by differential scanning calorimetry & Fourier transform-Infra red spectroscopy, Scanning electron microscopy and Atomic force microscopy. The average drug content, encapsulation efficiency and drug release studies were carried out for different formulations of Q-PLAN. The antioxidant activity of the formulated Q-PLAN nanoparticles was tested using DPPH assay.

Results: The formulation F3 (Quercetin 75 mg: PLA 200 mg) was found to be optimized formulation based on particle size analysis, Zeta potential, drug content, encapsulation efficiency and drug release studies. The mean diameter and zeta potential of optimized Q-PLAN and PLA nanoparticles were found to be 242±20 nm, 185±10 nm and-22.5±1.5 mV,-20.5±1.0 mV. The F3 formulation showed encapsulation efficiency of 73.3% and 5.5±0.06 mg/ml of actual drug loading. The F3 formulations showed 99.7% of drug release. The optimized Q-PLAN showed better scavenging effects when compared to the free quercetin.

Conclusions: The poor aqueous solubility and stability of the antioxidant molecule quercetin have been improved by entrapping the quercetin molecules into the PLA nanoparticles.

 

Downloads

Download data is not yet available.

Author Biographies

Bharathi Sambandam, Centre for Nanoscience and Technology Anna University Chennai

Centre for Nanoscience and Technology

Sathesh Kumar S, Department of Pharmaceutics School of Pharmaceutical Sciences VELS University, Chennai.

Department of Pharmaceutics

Arivarasan Ayyaswamy, Centre for Nanoscience and Technology Anna University Chennai

Centre for Nanoscience and Technology

Nagarjuna Yadav B V, Department of Pharmaceutics School of Pharmaceutical Sciences VELS University, Chennai.

Department of Pharmaceutics

Devasena Thiyagarajan, Centre for Nanoscience and Technology Anna University Chennai

Centre for Nanoscience and Technology

References

Kumari A, Yadav SK, Pakade YB, Singh B, Yadav SC. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf B 2010;80:184-92.

Nuengchamnong N, Hermans-Lokkerbol A, Ingkaninan K. Separation and detection of the antioxidant flavonoids, rutin and quercetin, using HPLC coupled on-line with colorimetric detection of antioxidant activity. Naresuan Univ J 2004;12:25–37.

Sorata Y, Takahama U, Kimura M. Protective effect of quercetin and rutin on photosensitized lysis of human erythrocytes in the presence of hematoporphyrin. Biochim Biophy Acta 1984;799:313-7.

Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. J Nutr 2008;24:703-10.

Borska S, Gebarowska E, Wysocka T, Drag-Zalesinska M, Zabel M. The effects of quercetin vs cisplatin on proliferation and the apoptotic process in A549 and SW1271 cell lines in in vitro conditions. Folia Morphol 2004;63:103-5.

Saito A, Sugisawa A, Umegaki K, Sunagawa H. Protective effects of quercetin and its metabolites on H2O2-induced chromosomal damage to WIL2-NS cells. Biosci Biotech Bioch 2004;68:271-6.

Moskaug JØ, Carlsen H, Myhrstad M, Blomhoff R. Molecular imaging of the biological effects of quercetin and quercetin-rich foods. Mech Ageing Dev 2004;125:315-24.

Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behavior of flavonoids: structure–activity relationships. Free Radic Biol Med 1997;22:749-60.

Pralhad T, Rajendrakumar K. Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. J Pharm Biomed Anal 2004;34:333-9.

Makris DP, Rossiter JT. Quercetin and rutin (quercetin 3-O-rhamnosylglucoside) thermal degradation in aqueous media under alkaline condition. In: Buttriss J, Saltmarsh M, Editors. Functional Foods-Claims and Evidence. Royal Society of Chemistry Press: London, UK; 2000. p. 216-38.

Hollman PC, Katan MB. Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol 1999;37:937-42.

Middleton EJ. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 1998;439:175-82.

Huk I, Brovkovych V, Nanobash VJ, Weigel G, Neumayer C, Partyka L, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study. Br J Surg 1998;85:1080-5.

Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996;20:933-56.

Shoskes DA. Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents. Transplantation 1998;66:147-52.

Dunnick JK, Hailey JR. Toxicity and carcinogenicity studies of quercetin, a natural component of foods. Fundam Appl Toxicol 1992;19:423-31.

Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of Flavonoids. Adv Pharmacol 1997;38:151-63.

Hollman PC, Van Trijp JM, Mengelers MJ, de VriesJH, Katan MB. Bioavailability of the dietary antioxidant flavonolquercetin in man. Cancer Lett 1997;114:139-40.

Young JF, Nielsen SE, Haraldsdottir J, Daneshvar B, Lauridsen ST, Knuthsen P, et al. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. Am J Clin Nutr 1999;69:87-94.

Lee SH, Zhang Z, Feng SS. Nanoparticles of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA–PGS) copolymers for protein drug delivery. Biomaterials 2007;28:2041-50.

Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliver Rev 2002;54:631-51.

Yuan F, Leuning M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in human tumor xenograft. Cancer Res 1994;54:3352-3356.

Lemos-Sennaa E, Wouessidjeweb D, Lesieura S, Duchênea D. Preparation of amphiphiliccyclodextrinnanospheres using the emulsification solvent evaporation method. Influence of the surfactant on preparation and hydrophobic drug loading. Int J Pharm 1998;170:119-28.

Vinogradov S, Batrakova E, Kabanov A. Poly(ethylene glycol)-polyethyleneimine Nano Gel TM particles: novel drug delivery systems for antisense oligonucleotides. Colloid Surf B 1999;16:291-304.

Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W, Muchimapura S. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomed 2008;4:70-8.

Zhang Y, Yang Y, Tang K, Hu X, Zou G. Physicochemical characterization and antioxidant activity of quercetin-loaded chitosan nanoparticles. J Appl Polym Sci 2008;107:891-7.

Wu TH, Yen FL, Lin LT, Tsai TR, Lin CC, Cham TM. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. Int J Pharm 2008;346:160-8.

Mehrotra P. Critical process parameters evaluation of modified nanoprecipitation method on lomustine nanoparticles and cytostatic activity study on L132 human cancer cell line. J Nanomed Nanotechnol 2012;3:1-8.

Kumar N, Bhandari P, Singh B, Bari SS. Antioxidant activity and ultra-performance LC-electrospray ionization-quadrupole time-of-flight mass spectrometry for phenolics-based fingerprinting of Rose species: Rosa damascena, Rosa bourboniana and Rosa brunonii. Food Chem Toxicol 2009;47:361-7.

Quintanar-Guerrero D, Allemann E, Fessi H, Doelker E. Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm 1998;24:1113-28.

Eerikainen H, Kauppine EI. Preparation of polymeric nanoparticles containing corticosteroid by a novel aerosol flow reactor method. Int J Pharm 2003;263:69-83.

Borghetti GS, Lula IS, Sinisterra RD, Bassani VL. Quercetin/β-Cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture. AAPS Pharm Sci Tech 2009;10:235-42.

Olejniczak S, Potrzebowski MJ. Solid state NMR studies and density functional theory (DFT) calculations of conformers of quercetin. Org Biomol Chem 2004;2:2315-22.

Mainardes RM, Gremiao MPD, Evangelista RC. Thermoanalytical study of praziquantel-loaded PLGA nanoparticles. Braz J Pharm Sci 2006;42:523-30.

Corrigan OI, Li X. Quantifying drug release from PLGA nanoparticulates. Eur J Pharm Sci 2009;37:477-85.

Joshi SA, Chavhan SS, Sawant KK. Rivastigmineloaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm 2010;76:189-99.

Mohanraj VJ, Chen Y. Nanoparticles: a review. Trop J Pharm Res 2006;5:561-73.

Ahsan F, Rivas IP, Khan MA, Torres Suarez AI. Targeting to macrophages: role of physicochemical properties of particulate carriers-liposomes and microspheres on the phagocytosis by macrophages. J Control Release 2002;79:29-40.

Galindo-Rodriguez S, Allemann E, Fessi H, Doelker E. Physicochemical parameters associated with nanoparticles formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm Res 2004;21:1428-39.

Song X, Zhao Y, Hou S, Xu F, Zhao R, He J, et al. Dual agents loaded PLGA nanoparticles: systematic study of particle size and drug entrapment efficiency. Eur J Pharm Biopharm 2008;69:445-53.

Song X, Zhao Y, Wu W, Bi Y, Cai Z, Chen Q, et al. PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: systematic study of particle size and drug entrapment efficiency. Int J Pharm 2008;350:320-9.

Astete CE, Sabliov CM. Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed 2008;17:247-89.

Chen J, Tian B, Yin X, Zhang Y, Hu D, Hu Z, et al. Preparation, characterization and transfection efficiency of cationic PE Gylated PLA nanoparticles as gene delivery systems. J Biotech 2007;130:107-13.

Qi L, Xu Z, Jiang X, Hu C, Zou X. Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr Res 2004;339:2693-700.

Hu J, Johnston KP, Williams RO. Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Dev Ind Pharm 2004;30:233-45.

Muthu MS, Singh S. Studies on biodegradable polymeric nanoparticles of risperidone: in vitro and in vivo evaluation. Nanomed 2008;3:305-19.

Gao H, Yang YW, Fan YG, Ma JB. Conjugates of poly (DL-lactic acid) with ethylenediamino or diethylenetriamino bridged bis(β-cyclodextrin)s and their nanoparticles as protein delivery systems. J Control Release 2006;112:301-11.

Michailova V, Berlinova I, Iliev P, Ivanov L, Titeva S, Momekov G, et al. Nanoparticles formed from PNIPAM-g-PEO copolymers in the presence of indomethacin. Int J Pharm 2010;384:154-64.

Sonaje K, Italia JL, Sharma G, Bhardwaj V, Tikoo K, Kumar MN. Development of biodegradable nanoparticles for oral delivery of ellagic acid and evaluation of their antioxidant efficacy against cyclosporine A-induced nephrotoxicity in rats. Pharm Res 2007;24:899-908.

Govender T, Riley T, Ehtezazi T, Garnett MC, Stolnik S, Illum L, et al. Defining the drug incorporation properties of PLA–PEG nanoparticles. Int J Pharm 2000;199:95-110.

Panyam J, Williams D, Dash A, Leslie-Pelecky D, Labhasetwar V. Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. J Pharm Sci 2004;93:1804-14.

Leo E, Brina B, Forni F, Vandelli MA. In vitro evaluation of PLA nanoparticles containing a lipophilic drug in water-soluble or insoluble form. Int J Pharm 2004;278:133-41.

Riihimaki LH, Vainio MJ, Heikura JMS, Valkonen KH, Virtanen VT, Vuorela PM. Binding of phenolic compounds and their derivatives to bovine and reindeer b-lactoglobulin. J Agric Food Chem 2008;56:7721-9.

Pool H, Quintanar D, Figueroa JD, Mano CM, Bechara JEH, Godinez LA, et al. Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. J Nanomater 2010;2012:145-380.

Sahoo NG, Kakran M, Shaal LA, Li L, Muller RH, Pal M, et al. Preparation and characterization of Quercetin nanocrystals. J Pharm Sci 2011;100(6):2379-90.

Published

01-05-2015

How to Cite

Sambandam, B., S. K. S, A. Ayyaswamy, N. Y. B V, and D. Thiyagarajan. “SYNTHESIS AND CHARACTERIZATION OF POLY D-L LACTIDE (PLA) NANOPARTICLES FOR THE DELIVERY OF QUERCETIN”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 5, May 2015, pp. 42-49, https://journals.innovareacademics.in/index.php/ijpps/article/view/5153.

Issue

Section

Original Article(s)