Defining the drug incorporation properties of PLA-PEG nanoparticles

The drug incorporation and physicochemical properties of PLA-PEG micellar l ike nanoparticles were examined in this study using a model water soluble d rug, procaine hydrochloride. Procaine hydrochloride was incorporated into n anoparticles made from a series of PLA-PEG copolymers with a fixed PEG bloc k (5 kDa) and a varying PLA segment (3-110 kDa). The diameter of the PLA-na noparticles increased from 27.7 to 174.6 nm, with an increase in the PLA mo lecular weight. However, drug incorporation efficiency remained similar thr oughout the series. Incorporation of drug into the smaller PLA-PEG nanopart icles made from 3:5, 15:5 and 30:5 copolymers did not influence the particl e size, while an increase was observed for the larger systems comprising 75 :5 and 110:5 copolymers. An increase in drug content for PLA-PEG 30:5 nanop articles was achieved by increasing the theoretical loading (quantity of in itially present drug). The size of these nanoparticles remained unchanged w ith the increasing drug content, supporting the proposed micellar type stru cture of the PLA-PEG 30:5 nanoparticles. The morphology of these systems re mained unchanged both at low and high theoretical drug loadings. Formulatio n variables, such as an increase in the aqueous phase pH, replacement with the base form of the drug and inclusion of lauric acid in the formulation d id not improve the incorporation efficiency of drug into PLA-PEG 30:5 nanop articles. While poly(aspartic acid) as a complexation agent did not improve the drug incorporation efficiency of procaine hydrochloride, it did so for another water soluble drug diminazene aceturate. This may be attributed to a stronger interaction of diminazene aceturate with poly(aspartic acid) re lative to procaine hydrochloride, as confirmed by thermodynamic analysis of isothermal titration calorimetric data. The drug incorporation and physico chemical characterisation data obtained in this study may be relevant in op timising the drug incorporation and delivery properties of these potential drug targeting carriers. (C) 2000 Elsevier Science B.V. All rights reserved .