PubMed · 15415039
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H WOHNLICH. 1950. [Lactic acid determination].. https://doi.org/10.1515/bchm2.1950.285.1-3.138
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Modeling release of small molecules from degradable microspheres is important to the design of controlled-release drug delivery systems. Release of small molecules from poly(d,l-lactide-co-glycolide) (PLG) particles is often controlled by diffusion of the drug through the polymer and by polymer degradation. In this study, a model is developed to independently determine the contributions of each of these factors by fitting the release of piroxicam from monodisperse 50-microm microspheres made with PLG of different initial molecular weights. The dependence of the drug diffusivity on polymer molecular weight was determined from in vitro release of piroxicam from monodisperse 10-microm PLG microspheres, and the polymer degradation rate was experimentally measured using gel permeation chromatography. The model also incorporates the effect of nonuniform drug distribution within the microspheres, which is obtained from confocal fluorescence microscopy. The model results agree well with experiments despite using only one fit parameter.
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The aim of the present work was to find a suitable method for the introduction of thiol functions on the surface of poly(DL-lactic acid) (PLA) nanoparticles. Three different approaches were investigated. The modification of the surface involves the activation of PLA carboxylic acid groups followed by the attack of a nucleophile such as cysteine (method #1) or cystamine (method #2 and #3) that provide thiol functions via an amide bond. For the conjugation with cystamine, a second reaction step is required to expose the sulfhydryl function of cystamine that is otherwise protected in a disulfide bond. 1,4-Dithio-DL-threitol (DTT) (method #2) or Tris(2-carboxyethyl)-phosphine hydrochloride (method #3) were evaluated for their ability to reduce this linkage. Method #1 allowed a maximum of 8.5+/-2.8 mmol of thiol functions per mol of PLA to be attached on the surface of the nanoparticles. Method #2 allowed the introduction of a greater number of thiol functions (up to 190+/-15 mmol per mol of PLA). However, this latter method has a major drawback: DTT interacts strongly with the nanoparticle matrix during the reduction step. Method #3 has the advantage over method #2 in that it allowed a significant number of thiol functions to be covalently bound to the particles (up to 107.6+/-0.6 mmol per mol of PLA) without the problem of undesired interaction between DTT and the nanoparticle matrix. The introduction of thiol groups onto the surface of PLA nanoparticles is possible with all three suggested methods. The method #3 provides a straight forward approach for the substitution of carboxylic acid groups with a high number of activated sulfhydryl at the surface of PLA nanoparticles.