Preparation of poly(D,L-lactide) nanoparticles assisted by amphiphilic poly(methyl methacrylate-co-methacrylic acid) copolymers

When co-precipitated with amphiphilic copolymers from DMSO, poly(D,L-lactid e) (PLA) can be readily converted into stable sub-200 nm nanoparticles by a ddition of an aqueous phase, free of any polymeric stabilizers such as poly (vinyl alcohol) or Poloxamer. In this work, the ability of random poly(meth yl methacrylate-co-methacrylic acid) copolymers (PMMA-co-MA) to stabilize P LA nanoparticles was demonstrated, and the properties of PLA/PMMA-co-MA nan oparticles were investigated. When co-precipitated with PMMA-co-MA, PLA was totally converted into nanoparticles using a polymer concentration in DMSO (C-P) below 17.6 mg ml(-1), and a PMMA-co-MA proportion above a critical v alue 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%, an d 0.5 mg mg(-1) PLA for X = 25% (for C-PLA = 16 mg ml(-1) DMSO). The nanopa rticle diameter was essentially independent of X, the proportion of PMMA-co -MA, and the PLA molecular weight, except for oligomers for which the nanop article diameter was smaller. It decreased when the organic phase was dilut ed (126 +/- 13 nm for C-P = 17.6 mg ml(-1), and 81 +/- 5 nm for C-P = 5.6 m g 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 functi onal groups to otherwise non-functionalized PLA nanoparticles. To illustrat e this, a conjugate of PMMA-co-MA(25) and biotin was synthesized, and used to prepare biotinylated nanoparticles that could be detected by fluorescenc e and transmission electron microscopy after infiltration into ligatured ra t small intestine.