PLA nanospheres

A subsequent study by Perez et al. (2001) investigated the use of poly (ethylene glycol)-(D,L-lactide) (PEG PLA) nanospheres for encapsulation... 

Poly(D,L-lactic acid) (PLA) nanospheres containing testosterone, with a particle size of 450 nm, were first produced by Vanderhoff et al. [83]. Microfluidization produced spherical particles of less than 200 nm with a narrow size distribution [84]. Krause et al. [85] produced PLA nanoparticles of 500 nm using sonication. The polymer and drug, triamcinolone acetonide, were dissolved in chloroform and emulsified, with sonication, for 45 minutes at 15 °C in a gelatin solution. The solvent was evaporated by heating to 40 °C for 45 minutes under continuous stirring. TEM... 

In another study, compounds 5 and 35 were incorporated in PEG/PLA nanospheres (NS) and nanocapsules (NC) [ 146]. In vitro drug release after high dilution of loaded... 

Figures. Spherical shape of nanosphetes evidenced by images of PLGA (A) and PEG5K-PLGASK (B) nanospheres taken with an atomic force microscopic (Nanoscope HI, Digital Instruments). (Reprinted, with permission, from Gief etal., 1994 Copyright (1995) AAAS.) (C) Picture of freeze-fractured (PEG20K), -PLA nanospheres taken by using transmission electron microscopy.

The location of PEG chains on the surface of PEG PLA nanospheres was checked by a degradation test (Bazile et al, 1995). The particles were incubated in sodium hydroxide solutions for different incubation times until total destruction, and the solutions were then neutralized by addition of phosphate buffer. The optical densities of these solutions (ODl) were measured after addition of iodine complexation agent. Control experiments... 

Tissue distribution studies 6 hr after injection of PEG-PLA nanospheres revealed that 53% of the injected dose was in the intestines, 11.3% in the liver, and 9.1% in plasma in the case of PLGA nanospheres, 52.2% of the dose was in the intestines, 20% in the liver, and 0.39% in plasma (Verrecchia et al, 1995). IBP is a drug with a fast hepatic metabolism and an intestinal and fecal elimination, and the tissue distribution of the drug is not modified in both cases (PEG-PLA and PLGA nanoparticles), except for the plasma residence time. 

Lidocaine was released from multiblock PEG3-PLA nanospheres over more than lOhr (Fig. 5 Peracchia et al, 1996). For these polymers, lower encapsulation efficiencies compared to those of diblock PEG-PLA particles were observed (Table II), probably due to the more hydrophilic nature of polymers containing several PEG blocks. The nanosphere size (measured by QELS) increases with the PEG molecular weight, presumably due to an increase in the thickness of the brush PEG coating with the PEG chain length. 

Polymeric micelles are expected to self-assemble when block copolymers are used for their preparation [28]. Micelles of biocompatible copolymer, viz., PEO with PLA or with PBLA, have been reported in the literature [29,30]. The synthesis of such nanospheres with functional groups on their surface is shown in Fig. 2. 

F urel. SchematicrepresentationofPEG-coatednaQospheres.Thecoatingsterichindrance should avoid blood protein (P) adsorption on the particle core, formed in a hydrophobic hiodegradahlepolymerR (PLA, PLGA,PCL, or PSA), (a) Nanosphere prepared from diblock PEG-R pol mer (h) nanosphere prepared from mrjltihlock PEG -R polymer. 

To prepare PEG-coated nanospheres as depicted in Fig. 1, first, amphiphilic bioerodible polymers (symbolized as PEG R), composed of a PEG block and a hydrophobic biodegradable block (R = PLA or PLGA), were synthesized. PEG-coated nanospheres were then formed by taking advantage of the different solubdities of R and PEG in aqueous and organic solutions (Spenlehauer et al., 1992 Grefet al., 1993a). Nanospheres were also formed with diblock PEG poly(E-caprolactone) (PEG PCL) and PEG-poly(sebacic acid) (PEG PSA) (Peracchia et al, 1996). 

One of the advantages of this type of nanospheres is that, owing to the amphiphilic nature of the block copolymers PEG-R and PEG -R, the use of other surfactants (not always biocompatible) can be avoided. This is not the case with PLA (Bazile et al, 1995) or PLGA (Gref et al, 1994) polymers, whatever the nanosphere preparation method. The use of surfactants such as poly(vinyl alcohol) (PVA) or Pluronic is necessary for the formation of PLA and PLGA nanoparticles, and thus additional washing steps are required to remove adsorbed surfactant. 

Water-soluble PLA-PEG copolymers with PLAiPEG ratios of 2 5 and 3 4 (PEG chains of 5 and 2kDa, respectively) were used to coat PLGA nanospheres and thus prepare sterically stabilized particles (Stolnik et al,... 

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