Positively-charged, porous, polysaccharide nanoparticles loaded with anionic molecules behave as 'stealth' cationic nanocarriers.
OBJECTIVE
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 (zeta) 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 zeta, whereas progressive BSA loading lightly decreased their zeta. 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.


CONCLUSIONS
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.
Inserm U646, Pôle pharmaceutique, CHU d'Angers, Université d'Angers, 10 rue André Boquel, 49100, Angers, France.
Archibald
A
Paillard
Catherine
C
Passirani
Patrick
P
Saulnier
Maya
M
Kroubi
Emmanuel
E
Garcion
Jean-Pierre
JP
Benoît
Didier
D
Betbeder
D000838:Anions / Q000737:chemistry / Q000494:pharmacology; D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D004339:Drug Compounding / Q000379:methods*; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011134:Polysaccharides / Q000737:chemistry* / Q000276:immunology; D013499:Surface Properties
D000838:Anions; D002412:Cations; D004337:Drug Carriers; D011134:Polysaccharides