Physicochemical Evaluation of Nanoparticles Assembled from Poly(lactic acid)−Poly(ethylene glycol) (PLA−PEG) Block Copolymers as Drug Delivery Vehicles

Abstract

Nanoparticles assembled from poly(D,L-lactic acid)-poly(ethylene glycol) (PLA-PEG) block copolymers may have a therapeutic application in site-specific drug delivery. A series of AB block copolymers based on a fixed PEG block (5 kDa) and a varying PLA segment (2-110 kDa) have been synthesized by the ring-opening polymerization of D,L-lactide using stannous octoate as a catalyst. These copolymers assembled to form spherical nanoparticles in aqueous media following precipitation from a water-miscible organic solvent. 1 H NMR studies of the PLA-PEG nanoparticles in D2O confirmed their core-shell structure, with negligible penetration of the hydrated PEG chains into the PLA core. The influence of the PLA block molecular weight on the hydrodynamic size and micellar aggregation number of the assemblies was determined by dynamic and static light scattering techniques. The hydrodynamic radius of the PLA-PEG 2:5-30:5 nanoparticles was solely dependent on the copolymer architecture and scaled linearly as NPLA 1/3 , where NPLA is the number of monomeric units in the PLA block. The PEG chains of the small PLA-PEG 2:5 and 3:5 assemblies appeared to be fairly splayed as a consequence of their relatively low aggregation number and high surface coverage. However, as NPLA was increased to 6 kDa the area available per PEG chain at the periphery of the shell decreased significantly and then remained fairly constant with further increases in the molecular weight of the PLA block. The aggregation number and hence particle size of nanoparticles produced from copolymers with a PLA block of 45 kDa or more was found to also depend on the concentration of copolymer dissolved in the organic phase during preparation. This suggested that that the PEG chains had little influence on the assembly of the higher molecular weight copolymers.

Drug transport to brain with targeted nanoparticles

“…57 The size of mPEG-PLA nanoparticles prepared with constant PEG 5000 was found to increase with the PLA block molecular weight. 59 With mPEG 5000 -PLA 2000-30000 nanoparticle diameters (from 26 to 64 nm in diameter) were shown to be independent of the copolymer concentration in the organic phase, whereas with higher PLA block molecular mass (45,000 Da) nanoparticle size was dependent on the copolymer concentration in the organic phase. 59 After preparation, nanoparticles can be freezedried in the presence of appropriate cryoprotector for longterm preservation.…”

“…59 With mPEG 5000 -PLA 2000-30000 nanoparticle diameters (from 26 to 64 nm in diameter) were shown to be independent of the copolymer concentration in the organic phase, whereas with higher PLA block molecular mass (45,000 Da) nanoparticle size was dependent on the copolymer concentration in the organic phase. 59 After preparation, nanoparticles can be freezedried in the presence of appropriate cryoprotector for longterm preservation. 51,62,63 Pegylated nanoparticle structure Nanoparticles prepared from mPEG-PLA/PLGA copolymers are constituted of a PLA/PLGA hydrophobic core surrounded by a hydrophilic PEG corona or outer shell.…”

“…In mPEG 5000 -PLA 2000-75000 nanoparticles, negligible penetration of the PEG into the solid-like PLA core was reported, whereas as much of 25% PEG is entrapped within the nanoparticle core in the case of mPEG 5000 -PLA 110000 . 59 It is likely that the [(water-in-oil) in water] solvent evaporation technique increases PEG entrapment, compared with the precipitation/solvent evaporation technique. 46 The water content of mPEG 5000 PLA 45000 nanoparticles (200 nm diameter) is around 30% compared with around 10% for PLA nanoparticles.…”

“…67 The PLA chain packing density increases with the PLA molecular weights due to an increase in the number of attractive hydrophobic interactions between lactic acid units. 59 In nanoparticles made of mPEG 5000 -PLA 2000 -3000 , PLA chains possess some mobility. 59 Because of the relatively high critical micellar concentration, these nanoparticles may dissociate upon dilution in blood.…”

Polymeric micelle-based bioassay with femtomolar sensitivity

“…The approximate micelle aggregation number (N agg ) can be calculated from the ratio of the average molecular weight of the micelle to the molecular weight of the block copolymer [14,15,16]. Dynamic Light Scattering experiments indicated that the average molecular weight of the micelle is ∼ 4.6×10 4 Dalton.…”