Asian Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Formulation and Optimization of Silymarin Loaded PLGA Nanoparticle for liver targeting


Affiliations
1 Department of Pharmaceutics, MET’s Institute of Pharmacy, Adgaon, Nashik, India
2 Department of Pharmaceutics, MET’s Institute of Pharmacy, Adgaon, Nashik, Maharashtra, India
3 MET’s Institute of Pharmacy, Adgaon, Nashik, India
     

   Subscribe/Renew Journal


The aim of present study was to prepare silymarin loaded PLGA polymeric nanoparticles for liver targeting by solvent evaporation method. Special attention was devoted to targeted drug delivery to liver and then the controlled release of drug from the polymeric nanoparticles. PLGA were employed as a bio-degradable polymer for targeting and controlled release of drug. The particle size of the resultant PN’s was mainly controlled by the agitation speed during the manufacturing process and polymer concentration. PLGA nanoparticles have the stability problem hence is PVA used as Surfactant as well as Stabilizing agent for the production of stable nanoparticles. Following particle size, zeta potential, and DSC and SEM analysis. The Silymarin nanoparticles were prepared with different ratio of polymer (PLGA), surfactant (PVA) and solvent (acetone) by using solvent evaporation method. The organic phase {drug + polymer (1:1, 1:3, 1:5) + solvent} was added to aqueous phase {water + PVA (1, 2, and 3 %)} and subjected for homogenization with different rpm. The formulation was heated with magnetic stirrer for evaporation of solvent for 2 hrs. After evaporation of solvent, the formulation was centrifuged and supernatant was collected by filtration and dried at room temperature. The formed nanoparticles were evaluated for particle size, entrapment efficiency and in vitro release. The Nanoparticle was obtained having Particle Size in between 422.4-294.3 nm. Entrapment Efficiency in between 74.30-99.8% and % drug release in between 73.53-98.67% which follows the sustained release behavior. From given Data it concludes that Nanoparticle containing PLGA exhibiting excellent sustained release characteristics and Entrapment efficiency and also Good particle Size. Hence After stability studies all formulations were found to be physically and chemically stable.

Keywords

Silymarin, PLGA, Polymeric Nanoparticle, PVA, Control Release.
Subscription Login to verify subscription
User
Notifications
Font Size


  • NCCAM. Research Report: National Center for Complementary and Alternative Medicine. 2003. Hepatitis C and Complementary and Alternative Medicine: 2003 Update; pp. 2–20.

  • Seeff LB, Curto TM, Szabo G, Everson GT, Bonkovsky HL, Dienstag JL, Shiffman ML, et al. Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology. 2008; 47: 605–612.

  • Strader DB, Bacon BR, Lindsay KL, La Brecque DR, Morgan T, Wright EC, Allen J, et al. Use of complementary and alternative medicine in patients with liver disease. Am J Gastroenterol. 2002; 97:2391–2397.

  • Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology. 2007; 132:1925–1936.

  • Freedman ND, Curto TM, Morishima C, Seeff LB, Goodman ZD, Wright EC, Sinha R, Everhart JE. the HALT-C Trial Group. Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. Alimentary Pharmacology and Therapeutics. 2010 2 NOV 2010.

  • Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy KR, Wahed AS, et al. Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. J Clin Pharmacol.2010;50:434–449.

  • Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, Doo E, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. 2012; 308:274–282

  • Wagner H. Plant constituents with antihepatotoxic activity. In: Beal JL, Reinhard E eds. Natural Products as Medicinal Agents. Stuttgart: Hippokrates-Verlag; 1981.

  • Bosisio E, Benelli C, Pirola O, et al. Effect of the flavanolignans of Silybummarianum L. on lipid peroxidation in rat livermicrosomes and freshly isolated hepatocytes. Pharmacol Res 1992; 25:147-154.

  • Baer-Dubowska W, Szaefer H, Drajka-Kuzniak V. Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica 1998; 28:735-743.

  • Halim AB, el-Ahmady O, Hassab-Allah S, et al. Biochemical effect of antioxidants on lipids and liver function in experimentally- induced liver damage. Ann ClinBiochem 1997; 34:656-663.

  • Campos R, Garido A, Guerra R, et al. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 1989; 55:417-419.

  • Fiebrich F, Koch H. Silymarin, an inhibitor of lipoxygenase. Experentia 1979; 35:150-152.

  • Dehmlow C, Erhard J, de Gischolar_main H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 1996; 23:749-754.

  • Fantozzi R, Brunelleschi S, Rubino A, et al. FMLP-activated neutrophils evoke histamine release from mast cells. Agents Actions 1986; 18:155-158.

  • Dehmlow C, Murawski N, de Gischolar_main H, et al. Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells. Life Sci 1996; 58:1591-1600.

  • De La Puerta R, Martinez E, Bravo L. Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol 1996; 48:968-970.

  • Sonnenbichler J, Zetl I. Biochemical effects of the flavanolignanesilibinin on RNA, protein and DNA synthesis in rat livers. In: Cody V, Middleton E, Harbourne JB, eds. Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological, and Structure-Activity Relationships. New York, NY; 1986:319-331.

  • Fuchs EC, Weyhenmeyer R, Weiner OH, et al. Effects of silibinin and of a synthetic analogue on isolated rat hepatic stellate cells and myofibroblasts.Arzneimittelforschung 1997; 26:643-649.

  • Deak G, Muzes G, Lang I. Immunomodulator effect of silymarin therapy in chronic alcoholic liver diseases. OrvHetil 1990:131:1291-1292, 1295-1296. [Article in Hungarian]

  • Lang I, Nekam K, Gonzalez-Cabello R. Hepatoprotective and immunological effects of antioxidant drugs. Tokai J ExpClin Med 1990; 15:123-127.

  • Vyas and Khar, Targeted and controlled drug delivery, first edition 2002

  • Jaya, A., et al. 2011, Targeting: New potential carriers for targeted drug delivery system, 8 (2), pp. 117-123.

  • Fabienne, D., et al. 2010, Review: To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery, Journal of Control Release, 148, pp. 135–146.

  • Pathak, Y. and Thassu, D. 2009, Drug delivery nanoparticles formulation and characterization, Drugs and Pharmaceutical Science Series, Informa health care, New York: USA, vol-191, pp. 4, 16-18, 56-59, 22-23, 27-28.

  • Kamel, A.O., et al. 2007, Preparation and characterization of acyclovir nanoparticles by double emulsion technique, EJBS, 23, pp.166-175.

  • Park, J., et al. 2009, PEGylated PLGA nanoparticles for the improved delivery of doxorubicin, Nanomedicine: NBM, 5, pp. 410-418.

  • Machado, S.R. and Evangelista, R.C. 2010, Development and characterization of Cefoxitin, J. Basic Appl. Pharm. Sci., 31 (3), pp. 193-202.

  • Kumar, P.V. and Jain, N.K. 2007, Suppression of agglomeration of ciprofloxacin-loaded human serum albumin nanoparticles, AAPS Pharm Sci Tech, 8 (1), pp. E1-E6.

  • Zhang, J.Y., et al. 2011, Preparation of the albumin nanoparticle system loaded with both paclitaxel and sorafenib and its evaluation in vitro and in vivo, J. Microencapsul., 28(6), pp.528–536.

  • Takashima, Y., etal. 2007, Spray-drying preparation of microparticles containing cationic PLGA nanospheres as gene carriers for avoiding aggregation of nanospheres, Int. J Pharma., 343, pp. 262-269.

  • Pandi, M., et al. 2011, Isolation and detection of taxol, an anticancer drug produced from Lasiodiplodiatheobromae, an endophytic fungus of the medicinal plant Morindacitrifolia, AJB, 10 (8), pp. 1428-1435.


Abstract Views: 220

PDF Views: 0




  • Formulation and Optimization of Silymarin Loaded PLGA Nanoparticle for liver targeting

Abstract Views: 220  |  PDF Views: 0

Authors

Irfan M. Saiyyad
Department of Pharmaceutics, MET’s Institute of Pharmacy, Adgaon, Nashik, India
D. S. Bhambere
Department of Pharmaceutics, MET’s Institute of Pharmacy, Adgaon, Nashik, Maharashtra, India
Sanjay Kshirsagar
MET’s Institute of Pharmacy, Adgaon, Nashik, India

Abstract


The aim of present study was to prepare silymarin loaded PLGA polymeric nanoparticles for liver targeting by solvent evaporation method. Special attention was devoted to targeted drug delivery to liver and then the controlled release of drug from the polymeric nanoparticles. PLGA were employed as a bio-degradable polymer for targeting and controlled release of drug. The particle size of the resultant PN’s was mainly controlled by the agitation speed during the manufacturing process and polymer concentration. PLGA nanoparticles have the stability problem hence is PVA used as Surfactant as well as Stabilizing agent for the production of stable nanoparticles. Following particle size, zeta potential, and DSC and SEM analysis. The Silymarin nanoparticles were prepared with different ratio of polymer (PLGA), surfactant (PVA) and solvent (acetone) by using solvent evaporation method. The organic phase {drug + polymer (1:1, 1:3, 1:5) + solvent} was added to aqueous phase {water + PVA (1, 2, and 3 %)} and subjected for homogenization with different rpm. The formulation was heated with magnetic stirrer for evaporation of solvent for 2 hrs. After evaporation of solvent, the formulation was centrifuged and supernatant was collected by filtration and dried at room temperature. The formed nanoparticles were evaluated for particle size, entrapment efficiency and in vitro release. The Nanoparticle was obtained having Particle Size in between 422.4-294.3 nm. Entrapment Efficiency in between 74.30-99.8% and % drug release in between 73.53-98.67% which follows the sustained release behavior. From given Data it concludes that Nanoparticle containing PLGA exhibiting excellent sustained release characteristics and Entrapment efficiency and also Good particle Size. Hence After stability studies all formulations were found to be physically and chemically stable.

Keywords


Silymarin, PLGA, Polymeric Nanoparticle, PVA, Control Release.

References