The stenlying effect of high hydrostatic pressure on thermally and hydrolytically labile nanosized carriers.
OBJECTIVE
To investigate whether high hydrostatic pressure (HHP) treatment allows the sterilization of thermosensitive polymer nanoparticle suspensions without jeopardizing their physicochemical integrity.


METHODS
Application of HHP was explored on a wide variety of thermosensitive poly(cyanoacrylate) nanoparticles, varying by their type (nanospheres or nanocapsules), by their preparation method (nanoprecipitation or emulsion/solvent evaporation), as well as by their surface characteristics. Physicochemical characterization before and after pressurization included turbidimetry, size measurement, zeta potential, scanning electron microscopy and infrared analysis. A sterility test also conducted according to pharmacopoeial requirements on an importantly contaminated nanoparticle suspension.


RESULTS
Poly(cyanoacrylate) nanoparticles appeared to be extremely baroresistant. Continuous or oscillatory HHP treatment up to 500 MPa during 30 min induced generally neither physical, nor chemical damage. However, precautions should be taken when surface modifiers are adsorbed onto nanoparticles, as a layer destabilization may occur. Finally, this process allowed the successful inactivation of vegetative bacteria, yeast, and fungi.


CONCLUSIONS
This work proposes HHP as a new method for polymer drug carriers sterilization, taking into account that further exploration in this area is needed to propose novel protocols for spores inactivation.
Brigger
Irène
I
Laboratory of Biopharmacy and Pharmaceutical Technology, UMR CNRS 8612, Faculty of Pharmacy, University of Paris XI, 5, rue J.B. Clement, 92296 Châtenay-Malabry, France.
Armand-Lefevre
Laurence
L
Chaminade
Pierre
P
Besnard
Madeleine
M
Rigaldie
Yohan
Y
Largeteau
Alain
A
Andremont
Antoine
A
Grislain
Luc
L
Demazeau
Gérard
G
Couvreur
Patrick
P
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D006874:Hydrostatic Pressure; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods*; D011108:Polymers; D013242:Sterilization / Q000295:instrumentation / Q000379:methods*; D013535:Suspensions
D004337:Drug Carriers; D011108:Polymers; D013535:Suspensions