Preparation of biodegradable, surface engineered PLGA nanospheres with enhanced lymphatic drainage and lymph node uptake.
OBJECTIVE
Nanospheres can be utilised for the targeting of drugs and diagnostic agents to the regional lymph nodes. The surface modification of model polystyrene, (PS), and poly(lactide-co-glycolide),(PLGA), nanospheres by poly(lactide)-poly(ethylene glycol), (PLA:PEG), copolymers has been assessed by in vitro characterisation and in vivo biodistribution studies following subcutaneous administration of the nanospheres to the rat.


METHODS
Three PLA:PEG copolymers were investigated, with PEG chain lengths of 750, 2000 and 5000 Da. The PLA:PEG copolymers were either coated onto the surface of PS and PLGA nanospheres or used as a co-precipitate in the formation of PLGA-PLA:PEG nanospheres. Coating of the nanospheres was confirmed by an increase in their particle size and a corresponding decrease in the surface potential. The kinetics of injection site drainage and lymph node retention was determined over a 24 hour time course for naked, coated and co-precipitated nanosphere systems.


RESULTS
Dependent on the surface characteristics, the distribution of the nanospheres can be significantly modified and the lymph node localisation dramatically enhanced by coating their surfaces with PLA:PEG copolymers or by producing co-precipitate nanospheres of PLGA and PLA:PEG.


CONCLUSIONS
A fully biodegradable nanosphere system has been developed with excellent lymph node targeting characteristics.
Hawley
A E
AE
Department of Pharmaceutical Sciences, University of Nottingham, University Park, U.K.
Illum
L
L
Davis
S S
SS
D000818:Animals; D001672:Biocompatible Materials; D007279:Injections, Subcutaneous; D019344:Lactic Acid; D008198:Lymph Nodes / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011060:Poloxalene; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011137:Polystyrenes; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution
D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D011137:Polystyrenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D011060:Poloxalene