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Preparation of poly(D,L-lactide) Nanoparticles Assisted by Amphiphilic Poly(methyl Methacrylate-Co-Methacrylic Acid) Copolymers

S Gautier, N Grudzielski, G Goffinet, S H de Hassonville, L Delattre, R Jérĵme

J Biomater Sci Polym Ed. 2001;12(4):429-50.

PMID: 11436978

Abstract:

When co-precipitated with amphiphilic copolymers from DMSO, poly(D,L-lactide) (PLA) can be readily converted into stable sub-200 nm nanoparticles by addition of an aqueous phase, free of any polymeric stabilizers such as poly(vinyl alcohol) or Poloxamer. In this work, the ability of random poly(methyl methacrylate-co-methacrylic acid) copolymers (PMMA-co-MA) to stabilize PLA nanoparticles was demonstrated, and the properties of PLA/PMMA-co-MA nanoparticles were investigated. When co-precipitated with PMMA-co-MA, PLA was totally converted into nanoparticles using a polymer concentration in DMSO (Cp) below 17.6 mg ml(-1), and a PMMA-co-MA proportion above a critical value depending on the content of MA repeating units (X). For instance, the lowest PMMA-co-MA proportion required was 0.9 mg mg(-1) PLA for X = 12%, and 0.5 mg mg(-1) PLA for X = 25% (for C(PLA) = 16 mg ml(-1) DMSO). The nanoparticle diameter was essentially independent of X, the proportion of PMMA-co-MA, and the PLA molecular weight, except for oligomers for which the nanoparticle diameter was smaller. It decreased when the organic phase was diluted (126 +/- 13 nm for Cp = 17.6 mg ml(-1), and 81 +/- 5 nm for C(P) = 5.6 mg ml(-1)). The time-dependence of the stability and the degradation of PLA/PMMA-co-MA nanoparticles was discussed. One of the main advantages of this technique is the ability to control surface properties and to bring functional groups to otherwise non-functionalized PLA nanoparticles. To illustrate this, a conjugate of PMMA-co-MA25 and biotin was synthesized, and used to prepare biotinylated nanoparticles that could be detected by fluorescence and transmission electron microscopy after infiltration into ligatured rat small intestine.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP25086151-D Poly(methyl methacrylate-co-methacrylic acid) Poly(methyl methacrylate-co-methacrylic acid) 25086-15-1 Price
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