Abstract
Poly(d,l-lactide-co-glycolide) nanoparticle (PLGA NP) have been broadly studied as a carrier for drug delivery system of peptides and proteins. However, negative surface charge of PLGA NP using only PLGA decreases bioavailability under oral administration. In this study, novel carriers for oral delivery system through an additional bioadhesive polymer, Eudragit was introduced. Our purpose is to prepare PLGA NP using bovine serum albumin (BSA) as a model drug and Eudragit and evaluate their physiochemical characteristics, eventually expand to peptide and protein drug such as insulin or exenatide. In this study, PLGA NP were spherical and the size was around 400–500 nm. The encapsulation efficiency (EE) of PLGA NP when prepared with only PLGA was the highest, approximately 95.3 %. The polydispersity index values were low approximately 0.1, which meant their size was regular. In mucoadhesion test, we knew PLGA NP prepared by using Eudragit RS or Eudragit RL had a high affinity to mucin particles through zeta-potential change of mucin particle to cover their surface. Also, PLGA NP did not show cytotoxicity against Caco-2 cells. Especially, BSA-loaded PLGA NP using Eudragit RS 100 prepared had high EE, low polydispersity index, spherical shape having a smooth surface, sustained release profile, non-cytotoxicity and bioadhesive effect.
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Aboubakar M, Puisieux F, Couvreur P, Vauthier C (1999) Physico-chemical characterization of insulin-loaded poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization. Int J Pharm 183:63–66
Agnihotri SA, Mallikarjuna NN, Aminabhavi TM (2004) Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Rel 100:5–28
Aksungur P, Demirbilek M, Denkbas EB, Vandervoort J, Ludwig A, Unlu N (2011) Development and characterization of Cyclosporine A loaded nanoparticles for ocular drug delivery: cellular toxicity, uptake, and kinetic studies. J Control Rel 151:286–294
Almeida AJ, Alpar HO, Brown MR (1993) Immune response to nasal delivery of antigenically intact tetanus toxoid associated with poly(l-lactic acid) microspheres in rats, rabbits and guinea-pigs. J Pharm Pharmacol 45:198–203
Arakawa T, Kita Y (2000) Stabilizing effects of caprylate and acetyltryptophanate on heat-induced aggregation of bovine serum albumin. Biochi Biophy Acta 1479:32–36
Bala I, Hariharan S, Kumar MN (2004) PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst 21:387–422
Bernkop-Schnurch A, Humenberger C, Valenta C (1998) Basic studies on bioadhesive delivery systems for peptide and protein drugs. Int J Pharm 165:217–225
Carino GP, Jacob JS, Mathiowitz E (2000) Nanosphere based oral insulin delivery. J Control Rel 65:261–269
Cegnar M, Kos J, Kristl J (2004) Cystatin incorporated in poly(lactide-co-glycolide) nanoparticles: development and fundamental studies on preservation of its activity. Eur J Pharm Sci 22:357–364
Cohen S, Yoshioka T, Lucarelli M, Hwang LH, Langer R (1991) Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres. Pharm Res 8:713–720
Damge C, Maincent P, Ubrich N (2007) Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. J Control Rel 117:163–170
Dandagi P, Kerur S, Mastiholimath V, Gadad A, Kulkarni A (2009) Polymeric ocular nanosuspension for controlled release of acyclovir. In vitro release and ocular distribution. Iran J Pharm Res 8:79–86
Das S, Suresh PK (2011) Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to amphotericin B. Nanomed Nanotechnol Biol Med 7:242–247
Das S, Suresh PK, Desmukh R (2010) Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomed Nanotechnol Biol Med 6:318–323
Desai MP, Labhasetwar V, Amidon GL, Levy RJ (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13:1838–1845
Dillen K, Vandervoort J, Van den Mooter G, Ludwig A (2006) Evaluation of ciprofloxacin-loaded Eudragit RS100 or RL100/PLGA nanoparticles. Int J Pharm 314:72–82
Dillen K, Bridts C, Van der Veken P, Cos P, Vandervoort J, Augustyns K, Stevens W, Ludwig A (2008) Adhesion of PLGA or Eudragit/PLGA nanoparticles to Staphylococcus and Pseudomonas. Int J Pharm 349:234–240
Eldridge JH, Hammond CJ, Meulbroek JA, Staas JK, Gilley RM, Tice TR (1990) Controlled Vaccine Release in the Gut-Associated Lymphoid-Tissues. 1. Orally-Administered Biodegradable Microspheres Target the Peyers Patches. J Control Rel 11:205–214
Estey T, Kang J, Schwendeman SP, Carpenter JF (2006) BSA degradation under acidic conditions: a model for protein instability during release from PLGA delivery systems. J Pharm Sci 95:1626–1639
Ganti V, Mengesha AE, Marszalek J, Youan BB (2010) Statistical analysis of low molecular mass heparin nanoencapsulation. Acta Pharma 60:281–293
Hao S, Wang B, Wang Y, Zhu L, Wang B, Guo T (2013) Preparation of Eudragit L 100-55 enteric nanoparticles by a novel emulsion diffusion method. Colloids Surf B Biointerfaces 108:127–133
Haznedar S, Dortunc B (2004) Preparation and in vitro evaluation of Eudragit microspheres containing acetazolamide. Int J Pharm 269:131–140
Hoffart V, Ubrich N, Simonin C, Babak V, Vigneron C, Hoffman M, Lecompte T, Maincent P (2002) Low molecular weight heparin-loaded polymeric nanoparticles: formulation, characterization, and release characteristics. Drug Dev Ind Pharm 28:1091–1099
Hombreiro-Perez M, Siepmann J, Zinutti C, Lamprecht A, Ubrich N, Hoffman M, Bodmeier R, Maincent P (2003) Non-degradable microparticles containing a hydrophilic and/or a lipophilic drug: preparation, characterization and drug release modeling. J Control Rel 88:413–428
Hu L, Tang X, Cui F (2004) Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol 56:1527–1535
Ichikawa H, Peppas NA (2003) Novel complexation hydrogels for oral peptide delivery: in vitro evaluation of their cytocompatibility and insulin-transport enhancing effects using Caco-2 cell monolayers. J Biomed Mater Res A 67:609–617
Igartua M, Hernandez RM, Esquisabel A, Gascon AR, Calvo MB, Pedraz JL (1998) Stability of BSA encapsulated into PLGA microspheres using PAGE and capillary electrophoresis. Int J Pharm 169:45–54
Jani P, Halbert GW, Langridge J, Florence AT (1989) The uptake and translocation of latex nanospheres and microspheres after oral administration to rats. J Pharm Pharmacol 41:809–812
Jani PU, Florence AT, Mccarthy DE (1992) Further histological evidence of the gastrointestinal absorption of polystyrene nanospheres in the rat. Int J Pharm 84:245–252
Jiao Y, Ubrich N, Hoffart V, Marchand-Arvier M, Vigneron C, Hoffman M, Maincent P (2002a) Anticoagulant activity of heparin following oral administration of heparin-loaded microparticles in rabbits. J Pharm Sci 91:760–768
Jiao Y, Ubrich N, Marchand-Arvier M, Vigneron C, Hoffman M, Lecompte T, Maincent P (2002b) In vitro and in vivo evaluation of oral heparin-loaded polymeric nanoparticles in rabbits. Circulation 105:230–235
Jung T, Kamm W, Breitenbach A, Kaiserling E, Xiao JX, Kissel T (2000) Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake? Eur J Pharm Biopharm 50:147–160
Katara R, Majumdar DK (2013) Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf B Biointerfaces 103:455–462
Katayama K, Kato Y, Onishi H, Nagai T, Machida Y (2003) Double liposomes: hypoglycemic effects of liposomal insulin on normal rats. Drug Dev Ind Pharm 29:725–731
Kim A, Yun MO, Oh YK, Ahn WS, Kim CK (1999) Pharmacodynamics of insulin in polyethylene glycol-coated liposomes. Int J Pharm 180:75–81
Kondo M, Niwa T, Okamoto H, Danjo K (2009) Particle characterization of poorly water-soluble drugs using a spray freeze drying technique. Chem Pharm Bull 57:657–662
Lopedota A, Trapani A, Cutrignelli A, Chiarantini L, Pantucci E, Curci R, Manuali E, Trapani G (2009) The use of Eudragit (R) RS 100/cyclodextrin nanoparticles for the transmucosal administration of glutathione. Eur J Pharm Biopharm 72:509–520
Malhotra M, Majumdar DK (2001) Permeation through cornea. Indian J Exp Biol 39:11–24
Maloy KJ, Donachie AM, O’Hagan DT, Mowat AM (1994) Induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in poly(lactide-co-glycolide) microparticles. Immunology 81:661–667
McClean S, Prosser E, Meehan E, O’Malley D, Clarke N, Ramtoola Z, Brayden D (1998) Binding and uptake of biodegradable poly-DL-lactide micro- and nanoparticles in intestinal epithelia. Eur J Pharm Sci 6:153–163
Morgan DML, Larvin VL, Pearson JD (1989) Biochemical-characterization of polycation-induced cyto-toxicity to human vascular endothelial-cells. J Cell Sci 94:553–559
Musumeci T, Ventura CA, Giannone I, Ruozi B, Montenegro L, Pignatello R, Puglisi G (2006) PLA/PLGA nanoparticles for sustained release of docetaxel. Int J Pharm 325:172–179
Nafee N, Taetz S, Schneider M, Schaefer UF, Lehr CM (2007) Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: effect of the formulation parameters on complexation and transfection of antisense oligonucleotides. Nanomed Nanotechnol Biol Med 3:173–183
Park MH, Baek JS, Lee CA, Cho CW (2013) Effect of chitosan on physicochemical properties of exenatide-loaded PLGA nanoparticles. J Pharm Invest 43:489–497
Peng ZG, Hidajat K, Uddin MS (2004) Adsorption of bovine serum albumin on nanosized magnetic particles. J Colloid Interface Sci 271:277–283
Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G (2002a) Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci 16:53–61
Pignatello R, Bucolo C, Spedalieri G, Maltese A, Puglisi G (2002b) Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application. Biomaterials 23:3247–3255
Roach P, Farrar D, Perry CC (2006) Surface tailoring for controlled protein adsorption: effect of topography at the nanometer scale and chemistry. J Ame Chem Soc 128:3939–3945
Saez V, Ramon JA, Caballero L, Aldana R, Cruz E, Peniche C, Paez R (2013) Extraction of PLGA-microencapsulated proteins using a two-immiscible liquid phases system containing surfactants. Pharm Res 30:606–615
Sakuma S, Suzuki N, Sudo R, Hiwatari K, Kishida A, Akashi M (2002) Optimized chemical structure of nanoparticles as carriers for oral delivery of salmon calcitonin. Int J Pharm 239:185–195
Takada S, Yamagata Y, Misaki M, Taira K, Kurokawa T (2003) Sustained release of human growth hormone from microcapsules prepared by a solvent evaporation technique. J Control Rel 88:229–242
Takeuchi H, Yamamoto H, Niwa T, Hino T, Kawashima Y (1996) Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes. Pharm Res 13:896–901
Takeuchi H, Yamamoto H, Kawashima Y (2001) Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Delivery Rev 47:39–54
Takeuchi H, Matsui Y, Yamamoto H, Kawashima Y (2003) Mucoadhesive properties of carbopol or chitosan-coated liposomes and their effectiveness in the oral administration of calcitonin to rats. J Control Rel 86:235–242
Takeuchi H, Thongborisute J, Matsui Y, Sugihara H, Yamamoto H, Kawashima Y (2005) Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems. Adv Drug Delivery Rev 57:1583–1594
Thongborisute J, Takeuchi H (2008) Evaluation of mucoadhesiveness of polymers by BIACORE method and mucin-particle method. Int J Pharm 354:204–209
Torres-Lugo M, Garcia M, Record R, Peppas NA (2002) Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins. J Control Rel 80:197–205
van der Merwe SM, Verhoef JC, Verheijden JH, Kotze AF, Junginger HE (2004) Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs. Eur J Pharm Biopharm 58:225–235
Wang YM, Mano JF (2006) Effect of structural relaxation at physiological temperature on the mechanical property of poly(L-lactic acid) studied by microhardness measurements. J Appl Polym Sci 100:2628–2633
Wu ZM, Zhou L, Guo XD, Jiang W, Ling L, Qian Y, Luo KQ, Zhang LJ (2012) HP55-coated capsule containing PLGA/RS nanoparticles for oral delivery of insulin. Int J Pharm 425:1–8
Xie S, Wang S, Zhao B, Han C, Wang M, Zhou W (2008) Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein-loaded solid lipid nanoparticles. Colloids Surf B 67:199–204
Yamaguchi Y, Takenaga M, Kitagawa A, Ogawa Y, Mizushima Y, Igarashi R (2002) Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled by hydrophilic additives. J Control Rel 81:235–249
Yan S, Xiaoqiang L, Shuiping L, Xiumei M, Ramakrishna S (2009) Controlled release of dual drugs from emulsion electrospun nanofibrous mats. Colloids Surf B 73:376–381
Yang A, Yang L, Liu W, Li Z, Xu H, Yang X (2007) Tumor necrosis factor alpha blocking peptide loaded PEG-PLGA nanoparticles: preparation and in vitro evaluation. Int J Pharm 331:123–132
Zhang D, Tan T, Gao L, Zhao W, Wang P (2007) Preparation of azithromycin nanosuspensions by high pressure homogenization and its physicochemical characteristics studies. Drug Dev Ind Pharm 33:569–575
Zhang X, Sun M, Zheng A, Cao D, Bi Y, Sun J (2012) Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration. Eur J Pharm Biopharm 45:632–638
Zhu KJ, Jiang HL, Du XY, Wang J, Xu WX, Liu SF (2001) Preparation and characterization of hCG-loaded polylactide or poly(lactide-co-glycolide) microspheres using a modified water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique. J Microencap 18:247–260
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This article does not contain any studies with human and animal subjects performed by any of the authors. All authors (M.H. Park, J.-S. Baek, C.-A. Lee, D.-C. Kim, C.W. Cho) declare that they have no conflict of interest. This study was financially supported by research fund of Chungnam National University.
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Park, MH., Baek, JS., Lee, CA. et al. The effect of Eudragit type on BSA-loaded PLGA nanoparticles. Journal of Pharmaceutical Investigation 44, 339–349 (2014). https://doi.org/10.1007/s40005-014-0129-0
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DOI: https://doi.org/10.1007/s40005-014-0129-0