Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid nanoparticles: Antibiotic resistance tests and HaCat and NIH/3T3 cell viability studies

Author(s)

Severino, Patricia ^{[1, 2, 3]} ; Chaud, Marco V. ^[4] ; Shimojo, Andrea ^[1] ; Antonini, Danilo ^[5] ; Lancelloti, Marcelo ^[5] ; Santana, Maria Helena A. ^[1] ; Souto, Eliana B. ^{[6, 7]}

Affiliation

^[1] State Univ Campinas UNICAMP, Sch Chem Engn, Biotechnol Proc Dev Lab, Sao Paulo - Brazil

^[2] Univ Tiradentes, BR-49010390 Aracaju - Brazil

^[3] Inst Technol & Res, BR-49010390 Aracaju - Brazil

^[4] Univ Sorocaba, Lab Biomat & Nanotechnol Dev & Evaluat Bioact Sub, BR-18023000 Sao Paulo - Brazil

^[5] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem, Sao Paulo - Brazil

^[6] Univ Coimbra FFUC, Fac Pharm, Dept Pharmaceut Technol, P-3000548 Coimbra - Portugal

^[7] Univ Coimbra, Ctr Neurosci & Cell Biol CNC, Polo Ciencias Saude, P-3000548 Coimbra - Portugal

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 129, p. 191-197, MAY 1 2015.
• Web of Science Citations: 27

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 500 bar 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 +/- 10 g for the loading capacity and 212.07 +/- 5.84% degree of swelling. The theological 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 +/- 20.42 nm, 0.241 +/- 0.050 and -34.8 +/- 0.55 my. 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. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 11/20801-2 - Polymixin B load in solid lipid nanoparticles for incorporation in mucoadhesive hydrogels for oral mucositis treatment
• Grantee: Patricia Severino
• Support Opportunities: Scholarships in Brazil - Post-Doctoral