Poly(ε-caprolactone) [poly(CL)] latexes and poly (D,L-lactide) [poly(D,L-Lc)] microspheres were prepared directly by ring-opening precipitation polymerization carried out in heptane-dioxane (4:1 v/v) mixed solvent in the presence of poly(dodecyl acrylate)-g-poly(ε-caprolactone) used as the surface active agent. This designed synthetic method yielded latexes and microspheres with narrow size distribution; poly(CL) latex D v / D n = 1.038 and for poly(D,LLc) microspheres D v / D n = 1.15. ( D v and D n denote the volume and number average diameters of particles.) The poly(CL) latex, synthesized by using CH 3 CH 2 OAl(CH 2 CH 3 ) 2 as initiator, had a narrow po ly m e r polydispersity of 1.11. Poly(D,L-Lc) microspheres, besides polymer with M w /M n = 1.05 contained some unreacted lactide. Adsorption of human serum albumin and human gamma globulins on both kinds of polyester particles was studied for their potential use as polypeptide and protein delivery systems.

Poly(l,l-lactide) microspheres were synthesized directly during the ring-opening precipitation polymerizations of l,l-lactide. The polymerizations were carried out in heptane−1,4-dioxane (4:1 v/v) mixed solvent in the presence of various poly(dodecyl acrylate)-g-poly(ε-caprolactone) copolymers (poly(DA−CL)) used as surface active agents. Copolymers with different molecular weights, different average number of poly(ε-caprolactone) grafts per macromolecule, and different molecular weights of these grafts were used. Poly(l,l-lactide) microspheres with number-average diameters (D̄ n) from 2.46 to 4.07 μm and with polydispersity parameters (D̄ v/D̄ n, where D̄ v denotes the volume-average diameter) from 1.08 to 1.45 were obtained. The dependence of D̄ n and D̄ v/D̄ n on the structure and on the concentration of poly(DA−CL) was investigated. The narrow diameter polydispersity (D̄ v/D̄ n = 1.08) was obtained when poly(DA−CL), containing an average of 1.3 poly(ε-caprolactone) grafts (with M̄ n = 4700 g/mol) per copolymer macromolecule, was used at a concentration of 1.6 g/L, i.e., below the critical concentration of micellization of this surface active agent (ccm = 5.1 g/L). Poly(l,l-lactide) microspheres contained from 1.5 to 6.6 wt % of the unreacted lactide. The optical purity of monomer (95.4%) and of the corresponding polylactide from microspheres (from 91.0% to 94.9%) indicated that polymerization in the investigated heterogeneous system proceeds with retention of configuration on the chiral carbon atom. The DSC studies revealed that the crystallinity of the poly(l,l-lactide) microspheres was strongly dependent on the thermal history of these materials and on the concentration of the surface active agent used for the polymerization. Microspheres partly composed of crystalline and/or amorphous poly(l,l-lactide) were obtained.

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Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a -CH 2 OH reactive side group in every structural unit. The hydroxyl groups in polyglycidol not only increase the hydrophilicity of this polymer but also allow for its modification, leading to polymers with carboxyl, amine, and vinyl groups, as well as to polymers with bonded aliphatic chains, sugar moieties, and covalently immobilized bioactive compounds in particular proteins. The paper describes the current state of knowledge on the synthesis of polyglycidols with various topology (linear, branched, and star-like) and with various molar masses. We provide information on polyglycidol-rich surfaces with protein-repelling properties. We also describe methods for the synthesis of polyglycidol-containing copolymers and the preparation of nano-and microparticles that could be derived from these copolymers. The paper summarizes recent advances in the application of polyglycidol and polyglycidol-containing polymers as drug carriers, reagents for diagnostic systems, and elements of biosensors.

New biodegradable/biocompatible ABC block copolymers, poly(ethylene oxide)‐b‐poly(glycidol)‐b‐poly(L,L‐lactide) (PEO‐PGly‐PLLA), were synthesized. First, PEO‐b‐poly(1‐ethoxyethylglycidol)‐b‐PLLA was synthesized by a successive anionic ring‐opening copolymerization of ethylene oxide, 1‐ethoxyethylglycidyl ether, and L,L‐lactide initiated with potassium 2‐methoxyethanolate. In the second step, the 1‐ethoxyethyl blocking groups of 1‐ethoxyethylglycidyl ether were removed at weakly acidic conditions leaving other blocks intact. The resulting copolymers were composed of hydrophilic and hydrophobic segments joined by short polyglycidol blocks with one hydroxyl group in each monomeric unit. These hydroxyl groups may be used for further copolymer transformations. The PEO‐PGly‐PLLA copolymers with a molecular weight of PLLA blocks below 5000 were water‐soluble. Above the critical micellar concentration (ranging from 0.05 to1.0 g/L, depending on the composition of copolymer), copolymers formed macromolecular micelles with a hydrophobic PLLA core and hydrophilic PEO shell. The diameters of the micelles were about 25 nm. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3750–3760, 2003

Formation of poly(L,L-lactide) (PLLA) and poly(D,L-lactide-co-glycolide) (PLGA) microparticles by dialysis from 1,4-dioxane, tetrahydrofuran (THF), acetonitrile, dimethyl sulfoxide (DMSO), and dimethylformamide (DMF) against water has been investigated. In some instances microparticles were obtained from a mixture of the above-mentioned polyesters and PLLA-block-polyglycidol-blockpoly(ethylene oxide) triblock copolymer containing a hydrophobic PLLA block as well as hydrophilic polyglycidol and poly(ethylene oxide) blocks, the former with functional -OH groups. The effects of the nature of polyester, solvent and concentration of triblock copolymer on particles morphology, size, size distribution, and degree of crystallinity have been determined. Dialysis of PLGA yielded particles in the form of microspheres regardless of the solvent. Diameters of these particles were in the range of 0.36 -1.77 µm and particles' diameter polydispersity ( D ) varied from 1.37 to 2.04, depending on the solvent. In the case of PLLA, microspheres were obtained only by dialysis from 1,4-dioxane solutions. Dialysis of PLLA solutions in THF, acetonitrile and DMF yielded particles in the form of microcrystals. In the case of dialysis of PLLA solutions in DMSO, the product was in form of crystalline flakes of c. 1 µm thickness. Microspheres composed of PLGA were amorphous. The degree of crystallinity of microparticles from PLLA was in the range of 39% -72%.

Dispersion polymerization of ε-caprolactone initiated with diethylaluminum alkoxide, carried out in the 1,4-dioxane:heptane (1:9 v/v) mixture at room temperature in the presence of poly(dodecyl acrylate)-g-poly(ε-caprolactone) used as the surface active agent, proceeds in two stages. In the first stage the growth of the poly(ε-caprolactone) chains is initiated in solution and, when the molecular weight of growing macromolecules comes close to 1000, the primary particles are nucleated and all propagating chains become incorporated into growing microspheres. In the second stage the polymerization process consists of propagation taking place inside microspheres into which monomer molecules diffuse from solution. During the first stage the apparent propagation rate constant is low and does not exceed 1 × 10-2 L·mol-1·s-1. In the second stage, due to the high local concentration of growing species confined in polymer particles, the apparent propagation rate constant becomes much higher. For monomer concentrations in the region from 3.9 × 10-1 mol·L-1 to 4.3 × 10-1 mol·L-1 and for initiator concentrations ranging from 3.4 × 10-3 mol·L-1 to 2.6 × 10-2 mol·L-1 the apparent propagation rate constant ( ) varied from 4.79 × 10-1 L·mol-1·s-1 to 6.5 × 10-2 L·mol-1·s-1.

Polylactide-b-polyglycidol-b-poly(ethylene oxide) terpolymers and their derivatives with carboxyl and 4-(phenylazo)phenyl labels in polyglycidol blocks were used for formation of nanoparticles. Nanoparticles were produced by self assembly of terpolymer macromolecules in water above the critical aggregation concentration and by dialysis of terpolymer solutions in 1,4-dioxane against water. For terpolymers with 4-(phenylazo)phenyl labels critical aggregation concentrations increased after irradiation with UV light (300 < lambda < 400 nm) inducing conformational change of the label from trans- to cis-conformation. Diameters of nanoparticles obtained by self-assembly of macromolecules ranged from 20 to 44 nm. Dialysis yielded nanoparticles with bimodal diameter distribution. One fraction had diameters below 35 nm and diameters of the second fraction were in a range from 350 to 2300 nm, depending on terpolymer structure. Mixtures of terpolymers with poly(L,L-lactide) and poly(D,D-lactide) blocks yielded nanoparticles with diameters from 350 to 440 nm. Pyrene was incorporated into nanoparticles by partition between solution and nanoparticles or directly during particle formation by dialysis. Monitoring of pyrene release from nanoparticles suggests that a fraction of this compound was entrapped into the polylactide core whereas the remaining one was located in the polyether rich shell. The release from shells is faster for nanoparticles made from copolymers with carboxyl labels in polyglycidol blocks.