Pullulan-based nanoparticles as carriers for transmucosal protein delivery

被引:65
作者
Dionisio, Marita [1 ,2 ]
Cordeiro, Clara [2 ,3 ,6 ]
Remunan-Lopez, Carmen [4 ]
Seijo, Begona [4 ]
da Costa, Ana M. Rosa [2 ,5 ]
Grenha, Ana [1 ,2 ]
机构
[1] IBB, Ctr Mol & Struct Biomed, CBME, P-8005139 Faro, Portugal
[2] Univ Algarve, Fac Sci & Technol, P-8005139 Faro, Portugal
[3] Univ Lisbon, Ctr Stat & Applicat, CEAUL, P-1749016 Lisbon, Portugal
[4] Univ Santiago de Compostela, Fac Pharm, Dept Pharm & Pharmaceut, NanoBioFar Grp, Santiago De Compostela 15782, Spain
[5] Algarve Chem Res Ctr, CIQA, P-8005139 Faro, Portugal
[6] Univ Algarve, Sch Hlth, CES, P-8000510 Faro, Portugal
关键词
Carrageenan; Chitosan; Drug delivery; Nanoparticles; Protein delivery; Pullulan; MICROENCAPSULATED CHITOSAN NANOPARTICLES; IN-VITRO; DRUG-DELIVERY; CHITOSAN/CARRAGEENAN NANOPARTICLES; CHEMICAL-STABILITY; POLYSACCHARIDES; INSULIN; SURFACE; CYTOTOXICITY; ENHANCEMENT;
D O I
10.1016/j.ejps.2013.04.018
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up. In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24 h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:102 / 113
页数:12
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