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Eur J Med Chem. 2014 Jun 23;81:28-34. doi: 10.1016/j.ejmech.2014.04.084. Epub 2014 May 2.

Solid lipid nanoparticles for hydrophilic biotech drugs: optimization and cell viability studies (Caco-2 & HEPG-2 cell lines).

Author information

1
School of Chemical Engineering, University of Campinas, UNICAMP, Campinas 13083-970, São Paulo, Brazil; Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, Office S.1, Locker S.27, P-4200-150 Porto, Portugal.
2
Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, Office S.1, Locker S.27, P-4200-150 Porto, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), P.O. Box 1013, 5000-911 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, UTAD, Vila Real, Portugal.
3
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Heyrovsky Sq. 2, 162 06 Prague, Czech Republic.
4
Laboratory for Development and Evaluation of Bioactive Substance, Sorocaba University, UNISO, Sorocaba 18023-000, Brazil.
5
School of Chemical Engineering, University of Campinas, UNICAMP, Campinas 13083-970, São Paulo, Brazil.
6
Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), P.O. Box 1013, 5000-911 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, UTAD, Vila Real, Portugal.
7
Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, Office S.1, Locker S.27, P-4200-150 Porto, Portugal; CEBIMED, Biomedicine Research Centre, Faculty of Health Sciences, Fernando Pessoa University (UFP-FCS), Rua Carlos da Maia, 296, 4200-150 Porto, Portugal; Institute of Biotechnology and Bioengineering, Centre of Genomics and Biotechnology University of Trás-os-Montes and Alto Douro (CGB-UTAD/IBB), P.O. Box 1013, P-5001-801 Vila Real, Portugal. Electronic address: eliana@ufp.edu.pt.

Abstract

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

KEYWORDS:

Caco-2 cell lines; Double emulsion; HEPG-2 cell lines; Hydrophilic biotech drugs; Lipid nanoparticles; insulin

PMID:
24819957
DOI:
10.1016/j.ejmech.2014.04.084
[Indexed for MEDLINE]

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