title: Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid nanoparticles: Antibiotic resistance tests and HaCat and NIH/3T3 cell viability studies.
abstract: Polymyxins are a group of antibiotics with a common structure of a cyclic peptide with a long hydrophobic tail. Polymyxin B sulphate (PLX) has cationic charge, which is an obstacle for the efficient loading into Solid Lipid Nanoparticles (SLN). In the present paper, we describe an innovative method to load PLX into SLN to achieve the sustained release of the drug. PLX was firstly cross-linked with sodium alginate (SA) at different ratios (1:1, 1:2 and 1:3 SA/PLX), and loaded into SLN produced by high pressure homogenization (HPH). Optimized SLN were produced applying 500bar pressure and 5 homogenization cycles. The best results were obtained with SA/PLX (1:1), recording 99.08±1.2% for the association efficiency of the drug with SA, 0.99±10g for the loading capacity and 212.07±5.84% degree of swelling. The rheological profile of aqueous SA solution followed the typical behaviour of concentrated polymeric solutions, whereas aqueous SA/PLX solution exhibited a gel-like dynamic behaviour. Micrographs show that SA/PLX depicted a porous and discontinuous amorphous phase in different ratios. The encapsulation efficiency of SA/PLX (1:1) in SLN, the mean particle diameter, polydispersity index and zeta potential were, respectively, 82.7±5.5%; 439.5±20.42nm, 0.241±0.050 and -34.8±0.55mV. The effect of SLN on cell viability was checked in HaCat and NIH/3T3 cell lines, and the minimal inhibitory concentrations (MIC) were determined in Pseudomonas aeruginosa strains. SA/PLX-loaded SLN were shown to be less toxic than free PLX. Minimal inhibitory concentrations (MIC) showed the presence of the cross-linker polymer-drug complex, and SLN were shown to enhance MIC in the evaluated strains.
authors: Biotechnological Processes Development Laboratory, School of Chemical Engineering, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil; University of Tiradentes and Institute of Technology and Research, Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil. Electronic address: pattypharma@gmail.com.
authors: Patrícia
authors: P
authors: Severino
authors: Laboratory of Biomaterials and Nanotechnology for the Development and Evaluation of Bioactive Substances, University of Sorocaba, Rodovia, Raposo Tavares km 92.5, 18023-000 Sorocaba, São Paulo, Brazil.
authors: Marco V
authors: MV
authors: Chaud
authors: Biotechnological Processes Development Laboratory, School of Chemical Engineering, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors: Andrea
authors: A
authors: Shimojo
authors: Biochemical Department, Biology Institute, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors: Danilo
authors: D
authors: Antonini
authors: Biochemical Department, Biology Institute, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors: Marcelo
authors: M
authors: Lancelloti
authors: Biotechnological Processes Development Laboratory, School of Chemical Engineering, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors: Maria Helena A
authors: MH
authors: Santana
authors: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: ebsouto@ff.uc.pt.
authors: Eliana B
authors: EB
authors: Souto
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011112:Polymyxin B / Q000494:pharmacology*
chemical_list: D000464:Alginates; D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D006603:Hexuronic Acids; D008055:Lipids; D020723:Glucuronic Acid; D011112:Polymyxin B
keywords: Drug delivery; High pressure homogenization; Polymyxin B sulphate; Pseudomonas aeruginosa; Sodium alginate; Solid lipid nanoparticles