FORMULATION OF L-ASPARAGINASE-LOADED POLY(LACTIDE-CO-GLYCOLIDE) NANOPARTICLES - INFLUENCE OF POLYMER PROPERTIES ON ENZYME LOADING, ACTIVITYAND IN-VITRO RELEASE

This paper describes the preparation and characterisation of poly(lact ide-co-glycolide) (PLG) nanoparticles containing the enzyme L-asparagi nase. L-Asparaginase was encapsulated in PLG nanospheres using a water -in-oil-in-water solvent evaporation technique. The effect of the copo lymer molecular weight and the presence of carboxyl-end groups in the copolymer chain on the physicochemical and in vitro release properties of the nanoparticles was investigated, Results indicated that size, e ncapsulation efficiency and in vitro release properties (enzymatic act ivity retention and protein quantification) of the nanoparticles were affected by the PLG molecular weight. As expected, nanoparticles made of high-molecular-weight PLG had a larger size, a higher loading and a slower release rate than those made of low-molecular-weight PLG, Neve rtheless, the most relevant factor affecting the entrapment and releas e of L-asparaginase from PLG nanoparticles was the presence of free ca rboxyl-end groups in the PLG chain. The nanoparticles made of PLG with free carboxyl-end groups had a high protein loading (4.86%, w/w) and provided a continuous delivery of the active enzyme for 20 days. Howev er, the enzyme loading was lower (2.65%, w/v) and no active enzyme was detected in the release medium after a 14-day incubation period when nanoparticles were made of PLG with carboxyl-end groups esterified. Th ese results give evidence of the potential of PLG nanospheres for the continuous delivery of L-asparaginase for extended periods of time and show the effect of the PLG chain end-groups in the amount and activit y of the enzyme loaded into the nanospheres. (C) 1998 Elsevier Science B.V.