Positively-Charged, Porous, Polysaccharide Nanoparticles Loaded with Anionic Molecules Behave as ‘Stealth' Cationic Nanocarriers

• Published in: Pharmaceutical research 2010-01, Vol.27 (1), p.126-133
• Main Authors: Paillard, Archibald, Passirani, Catherine, Saulnier, Patrick, Kroubi, Maya, Garcion, Emmanuel, Benoît, Jean-Pierre, Betbeder, Didier
• Format: Article
• Language: English
• Subjects: Anions; Anions - chemistry; Anions - pharmacology; Bioavailability; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cations; Cations - chemistry; Cations - pharmacology; Complement Activation; Complement Activation - drug effects; Drug Carriers; Drug Carriers - chemical synthesis; Drug Carriers - pharmacology; Drug Compounding; Drug Compounding - methods; Electrophoresis; Electrophoresis - methods; Emerging diseases; General pharmacology; Human health and pathology; Humans; Life Sciences; Lipids; Medical Law; Medical sciences; Models, Chemical; Nanoparticles; Nanoparticles - chemistry; Particle Size; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Polymers; Polysaccharides; Polysaccharides - chemistry; Polysaccharides - immunology; Proteins; Research Paper; Surface Properties
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9986-z

Purpose Stealth nanoparticles are generally obtained after modifying their surface with hydrophilic polymers, such as PEG. In this study, we analysed the effect of a phospholipid (DG) or protein (BSA) inclusion in porous cationic polysaccharide (NP⁺) on their physico-chemical structure and the effect on complement activation. Methods NP⁺s were characterised in terms of size, zeta potential (ζ) and static light scattering (SLS). Complement consumption was assessed in normal human serum (NHS) by measuring the residual haemolytic capacity of the complement system. Results DG loading did not change their size or ζ, whereas progressive BSA loading lightly decreased their ζ. An electrophoretic mobility analysis study showed the presence of two differently-charged sublayers at the NP⁺ surface which are not affected by DG loading. Complement system activation, studied via a CH50 test, was suppressed by DG or BSA loading. We also demonstrated that NP⁺s could be loaded by a polyanionic molecule, such as BSA, after their preliminary filling by a hydrophobic molecule, such as DG. Conclusion These nanoparticles are able to absorb large amounts of phospholipids or proteins without change in their size or zeta potential. Complement studies showed that stealth behaviour is observed when they are loaded and saturated either with anionic phospholipid or proteins.