Effect of Formulation Variables for the Production of WGA-Grafted, Levodopa-Loaded PLGA Nanoparticles

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Abstract:

Levodopa is used for the treatment of Parkinson’s disease (PD) for the last few decades. However, adverse reactions such as dyskinesia, somnolence, nausea, itching, rash, as well as the need for frequent dosing and low bioavailability problems affect the success of the treatment. To prevent side effects caused by conventional therapy, a nanoparticular drug delivery system has been developed, in which receptors are constantly stimulated, and the frequency of dosing is reduced. In this study, levodopa was loaded in Poly lactic-co-glycolic acid (PLGA) nanoparticles (NP) which modified with Wheat Germ Agglutinin (WGA) To increase the effectiveness of levodopa, reduce its side effects and apply to the nasal area which is an alternative way for brain targeting with lower doses. To obtain the optimum levodopa loaded PLGA nanoparticles, the effect of some formulation variables such as polyvinyl alcohol (PVA) concentration, homogenization speed, polymer amount and molecular weight, and levodopa content on the entrapment efficiency (EE) and particle size of the nanoparticles were investigated. Besides these variables, the effect of different parameters on the WGA binding constant was also searched. In addition to in vitro release studies, Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectrophotometer (FT-IR), and Transmission electron microscopy (TEM) analysis were used in the characterization of nanoparticles. Among all formulations, A2 and A8a which was produced with different molcular weights of PLGA, different added levodopa amounts and with different homogenization speeds were chosen as optimum formulations due to their sustained release properties and the ability to release 80 % of their drug content.WGA binding constant was found 78.20 % for A8a-1 and 95 % for A2-1. In this study, we aimed to determine the effect of different formulation parameters on the development of levodopa loaded and WGA grafted PLGA nanoparticles and on the quality characteristics of nanoparticle formulations such as particle size, zeta potential, and EE. In this paper, our results are demonstrated for a better understanding of the effect of process parameters on the development of nanoparticle-based drug delivery systems by using the double-emulsion solvent evaporation technique and on WGA binding of drug-loaded PLGA nanoparticles.

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[1] Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology 2009;72:S1-S136.

DOI: 10.1212/wnl.0b013e3181a1d44c

Google Scholar

[2] Salat D, Tolosa E. Levodopa in the treatment of Parkinson's disease: current status and new developments. J Parkinsons Dis 2013;3:255-69.

Google Scholar

[3] Rezak M. Current pharmacotherapeutic treatment options in Parkinson's disease. Disease-a-month 2007;53:214-22.

DOI: 10.1016/j.disamonth.2007.05.002

Google Scholar

[4] Kura AU, Al Ali SH, Hussein MZ, Fakurazi S, Arulselvan P. Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent. International journal of nanomedicine 2013;8:1103-10.

DOI: 10.2147/ijn.s39740

Google Scholar

[5] Comoglu T, Arisoy S, Akkus ZB. Nanocarriers for Effective Brain Drug Delivery. Current Topics in Medicinal Chemistry 2017;17:1490-506.

DOI: 10.2174/1568026616666161222101355

Google Scholar

[6] Dodov MG, Calis S, Crcarevska M, Geskovski N, Petrovska V, Goracinova K. Wheat germ agglutinin-conjugated chitosan–Ca–alginate microparticles for local colon delivery of 5-FU: Development and in vitro characterization. International journal of pharmaceutics 2009;381:166-75.

DOI: 10.1016/j.ijpharm.2009.06.037

Google Scholar

[7] Öztürk AA, Çinar Nİ, Yenilmez E. Development of nano-sized ketoprofen lysine incorporated Eudragit® S100 nanomedicine by double emulsion solvent evaporation and in vitro characterization. J Pharm Pharmacogn Res 2019;7:47-58.

Google Scholar

[8] Iqbal M, Zafar N, Fessi H, Elaissari A. Double emulsion solvent evaporation techniques used for drug encapsulation. International Journal of Pharmaceutics 2015;496:173-90.

DOI: 10.1016/j.ijpharm.2015.10.057

Google Scholar

[9] Amasya G, Badilli U, Aksu B, Tarimci N. Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion—Solvent evaporation method. European Journal of Pharmaceutical Sciences 2016;84:92-102.

DOI: 10.1016/j.ejps.2016.01.003

Google Scholar

[10] Ding S, Serra CA, Vandamme TF, Yu W, Anton N. Double emulsions prepared by two–step emulsification: History, state-of-the-art and perspective. Journal of controlled release 2019;295:31-49.

DOI: 10.1016/j.jconrel.2018.12.037

Google Scholar

[11] Bouriche S, Cózar-Bernal MJ, Rezgui F, Álvarez AMR, González-Rodríguez ML. Optimization of preparation method by W/O/W emulsion for entrapping metformin hydrochloride into poly (lactic acid) microparticles using Box-Behnken design. Journal of Drug Delivery Science and Technology 2019; 51:419-29.

DOI: 10.1016/j.jddst.2019.03.011

Google Scholar

[12] Sarkar P, Bhattacharya S, Pal TK. Application of statistical design to evaluate critical process parameters and optimize formulation technique of polymeric nanoparticles. Royal Society open science 2019;6:190896.

DOI: 10.1098/rsos.190896

Google Scholar

[13] Sonvico F, Clementino A, Buttini F, Colombo G, Pescina S, Staniscuaski Guterres S, et al. Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting. Pharmaceutics 2018;10.

DOI: 10.3390/pharmaceutics10010034

Google Scholar

[14] Brauner B, Semmler J, Rauch D, Nokaj M, Haiss P, Schwarz P, et al. Trimethoprim-Loaded PLGA Nanoparticles Grafted with WGA as Potential Intravesical Therapy of Urinary Tract Infections—Studies on Adhesion to SV-HUCs Under Varying Time, pH, and Drug-Loading Conditions. ACS omega 2020;5:17377-84.

DOI: 10.1021/acsomega.0c01745

Google Scholar

[15] Pandey AN, Rajpoot K, K Jain SKJ. Using 5-fluorouracil-encored plga nanoparticles for the treatment of colorectal cancer: the in-vitro characterization and cytotoxicity studies. Nanomedicine Journal 2020;7:211-24.

Google Scholar

[16] Arisoy S, Sayiner O, Comoglu T, Onal D, Atalay O, Pehlivanoglu B. In Vitro and in Vivo Evaluation of Levodopa Loaded Nanoparticles for Nose to Brain Delivery. Pharmaceutical Development and Technology 2020:1-31.

DOI: 10.1080/10837450.2020.1740257

Google Scholar

[17] Shin M, Kim HK, Lee H. Dopamine‐loaded poly (d, l‐lactic‐co‐glycolic acid) microspheres: New strategy for encapsulating small hydrophilic drugs with high efficiency. Biotechnology progress 2014;30:215-23.

DOI: 10.1002/btpr.1835

Google Scholar

[18] Zeini D, Khoshkenar P, Rabiee M. The influence of formulation and process parameters on the morphology, size and release profile of L-dopa-loaded poly lactic-co-glycolic acid (PLGA) microspheres. Open Conf Proc J2012. pp.1-7.

DOI: 10.2174/2210289201203010001

Google Scholar

[19] Weissenbock A, Wirth M, Gabor F. WGA-grafted PLGA-nanospheres: preparation and association with Caco-2 single cells. J Control Release 2004;99:383-92.

DOI: 10.1016/j.jconrel.2004.07.025

Google Scholar

[20] Arisoy S, Sayiner Ö, Comoglu T. Evaluation of release of L-DOPA from PLGA nanopartıcles with different in vitro release methods by an optimized HPLC method. Bezmialem Science (2020).

DOI: 10.14235/bas.galenos.galenos.2020.3860

Google Scholar

[21] Portaccio M, Menale C, Diano N, Serri C, Mita DG, Lepore M. Monitoring production process of cisplatin-loaded PLGA nanoparticles by FT-IR microspectroscopy and univariate data analysis. Journal of Applied Polymer Science 2015;132:n/a-n/a.

DOI: 10.1002/app.41305

Google Scholar

[22] Cortesi R, Esposito E, Drechsler M, Pavoni G, Cacciatore I, Sguizzato M, et al. L-dopa co-drugs in nanostructured lipid carriers: A comparative study. Mater Sci Eng C Mater Biol Appl 2017;72:168-76.

DOI: 10.1016/j.msec.2016.11.060

Google Scholar

[23] Gambaryan P, Kondrasheva I, Severin E, Guseva A, Kamensky A. Increasing the Efficiency of Parkinson's Disease Treatment Using a poly (lactic-co-glycolic acid)(PLGA) Based L-DOPA Delivery System. Experimental neurobiology 2014;23:246-52.

DOI: 10.5607/en.2014.23.3.246

Google Scholar

[24] Zhou YZ, Alany RG, Chuang V, Wen J. Optimization of PLGA nanoparticles formulation containing L-DOPA by applying the central composite design. Drug Dev Ind Pharm 2013;39:321-30.

DOI: 10.3109/03639045.2012.681054

Google Scholar

[25] Mainardes RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. International Journal of Pharmaceutics 2005; 290: 137-44.

DOI: 10.1016/j.ijpharm.2004.11.027

Google Scholar

[26] Cao J, Choi J-S, Oshi MA, Lee J, Hasan N, Kim J, et al. Development of PLGA micro- and nanorods with high capacity of surface ligand conjugation for enhanced targeted delivery. Asian Journal of Pharmaceutical Sciences 2019;14:86-94.

DOI: 10.1016/j.ajps.2018.08.008

Google Scholar

[27] Haggag YA, Faheem AM, Tambuwala MM, Osman MA, El-Gizawy SA, O'Hagan B, et al. Effect of poly(ethylene glycol) content and formulation parameters on particulate properties and intraperitoneal delivery of insulin from PLGA nanoparticles prepared using the double-emulsion evaporation procedure. Pharmaceutical Development and Technology 2018;23:370-81.

DOI: 10.1080/10837450.2017.1295066

Google Scholar

[28] Wang J, Helder L, Shao J, Jansen JA, Yang M, Yang F. Encapsulation and release of doxycycline from electrospray-generated PLGA microspheres: Effect of polymer end groups. International journal of pharmaceutics 2019;564:1-9.

DOI: 10.1016/j.ijpharm.2019.04.023

Google Scholar

[29] Budhian A, Siegel SJ, Winey KI. Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content. International Journal of Pharmaceutics 2007;336:367-75.

DOI: 10.1016/j.ijpharm.2006.11.061

Google Scholar

[30] Sharma S, Lohan S, Murthy R. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug development and industrial pharmacy 2014;40:869-78.

DOI: 10.3109/03639045.2013.789051

Google Scholar

[31] Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study. Asian Journal of Pharmaceutical Sciences 2016;11:404-16.

DOI: 10.1016/j.ajps.2015.09.004

Google Scholar

[32] Voigt N, Henrich-Noack P, Kockentiedt S, Hintz W, Tomas J, Sabel BA. Surfactants, not size or zeta-potential influence blood-brain barrier passage of polymeric nanoparticles. Eur J Pharm Biopharm 2014;87:19-29.

DOI: 10.1016/j.ejpb.2014.02.013

Google Scholar

[33] Jo DH, Kim JH, Lee TG, Kim JH. Size, surface charge, and shape determine therapeutic effects of nanoparticles on brain and retinal diseases. Nanomedicine 2015;11:1603-11.

DOI: 10.1016/j.nano.2015.04.015

Google Scholar

[34] Rampino A, Borgogna M, Blasi P, Bellich B, Cesàro A. Chitosan nanoparticles: Preparation, size evolution and stability. International Journal of Pharmaceutics 2013;455:219-28.

DOI: 10.1016/j.ijpharm.2013.07.034

Google Scholar

[35] Lamprecht A, Ubrich N, Hombreiro Pe´rez M, Lehr CM, Hoffman M, Maincent P. Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique. International Journal of Pharmaceutics 2000;196:177–82.

DOI: 10.1016/s0378-5173(99)00422-6

Google Scholar

[36] Mo Y, Lim LY. Mechanistic Study of the Uptake of Wheat Germ Agglutinin-Conjugated PLGA Nanoparticles by A549 Cells. JOURNAL OF PHARMACEUTICAL SCIENCES 2004;93:20-8.

DOI: 10.1002/jps.10507

Google Scholar

[37] Wang C, Ho PC, Lim LY. Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells. International Journal of Pharmaceutics 2010;400:201-10.

DOI: 10.1016/j.ijpharm.2010.08.023

Google Scholar

[38] Obaidat R, Al-Shar'i N, Tashtoush B, Athamneh T. Enhancement of levodopa stability when complexed with β-cyclodextrin in transdermal patches. Pharmaceutical Development and Technology 2018;23:986-97.

DOI: 10.1080/10837450.2016.1245319

Google Scholar

[39] Mohanraj K, Sethuraman S, Krishnan UM. Development of poly(butylene succinate) microspheres for delivery of levodopa in the treatment of Parkinson's disease. J Biomed Mater Res B Appl Biomater 2013;101:840-7.

DOI: 10.1002/jbm.b.32888

Google Scholar

[40] Pecora R. Dynamic Light Scattering Measurement of Nanometer Particles in Liquids. Journal of Nanoparticle Research 2000;2:123-31.

Google Scholar

[41] Ravani L, Sarpietro MG, Esposito E, Di Stefano A, Sozio P, Calcagno M, et al. Lipid nanocarriers containing a levodopa prodrug with potential antiparkinsonian activity. Materials Science and Engineering: C 2015;48:294-300.

DOI: 10.1016/j.msec.2014.12.014

Google Scholar