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-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.
Gautier
S
S
Center for Education and Research on Macromolecules, University of Liege, Belgium. sgautier@ulg.ac.be
Grudzielski
N
N
Goffinet
G
G
de Hassonville
S H
SH
Delattre
L
L
Jérĵme
R
R
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000302:isolation & purification; D001673:Biodegradation, Environmental; D011232:Chemical Precipitation; D004121:Dimethyl Sulfoxide; D004355:Drug Stability; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000648:ultrastructure; D008422:Materials Testing; D008854:Microscopy, Electron; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000302:isolation & purification / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D001672:Biocompatible Materials; D011091:Polyesters; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C033616:poly(lactide); D004121:Dimethyl Sulfoxide