Mariusz Gadzinowski

Synthesis of Bioerodible Poly(ε-caprolactone) Latexes and Poly(D, L-lactide) Microspheres by Ring-Opening Polymerization:

Poly(ε-caprolactone) [poly(CL)] latexes and poly(D,L-lactide) [poly(D,L-Lc)] microspheres were prepared directly by ring-opening precipita tion 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/Dn = 1.038 and for poly(D,L- Lc) microspheres Dv/Dn = 1.15. (Dv and Dn denote the volume and number average diameters of particles.) The poly(CL) latex, synthesized by using CH3CH2OAl(CH2CH3) 2 as initiator, had a narrow polymer polydispersity of 1.11. Poly(D,L-Lc) microspheres, besides polymer with Mw/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.

Polyesters from lactides and ε-caprolactone. Dispersion polymerization versus polymerization in solution

Polymerizations of lactides and ∈-caprolactone, carried out in 1,4-dioxane:-heptane mixtures in the presence of poly(dodecyl acrylate)-g-poly(∈ -caprolactone) surface active agent, yield polymers in the form of microspheres. Polymerizations are initiated in solution. Shortly after initiation particles are nucleated and the main part of propagation proceeds in heterogeneous systems which consist of growing microspheres suspended in the 1,4-dioxane-heptane-monomer media. These dispersion polymerizations differ in many aspects from the corresponding polymerizations in solution. Suspensions of microspheres are significantly less viscous than polymer solutions with the same polymer content. For example, viscosity of suspension of polylactide microspheres (microsphere diameters D n =2.7 μm) in heptane is 14 times lower than that of the THF solution of the same polylactide (polymer content in suspension and in solution 5 wt%). High local concentrations of active centers and monomers inside microspheres result in fast polymerization. For polymerizations of ∈-caprolactone in dispersed systems, a given degree of monomer conversion is achieved from 10 to 20 times earlier than for the corresponding polymerizations in solution. Dispersion polymerizations yield polylactides and poly(∈-caprolactone) with 1.05 10) are obtained in polymerizations carried out in the presence of a surface active agent with a ratio of molecular weight of poly(∈-caprolactone) grafts and molecular weight of poly(dodecyl acrylate)-g-poly(∈-caprolactone) copolymer close to 0.23. The microspheres can be isolated from suspension by gravitational sedimentation. Depending on the post-synthesis treatment it is possible to obtain poly(L,L-lactide) microspheres with controlled degree of crystallinity.

Latexes and microspheres by ring-opening polymerization. Polymerization of cyclic esters

Abstract Latexes and microspheres were synthesized by pseudoanionic polymerization of lactides initiated with tin(II) 2-ethylhexanoate and pseudoanionic and anionic polymerization of ϵ-caprolactone initiated with (CH3CH2)2AlOCH2CH3 and (CH3)3SiONa, respectively. Polymerizations were carried out in 1,4-dioxane/heptane mixtures with poly(dodecyl acrylate)-g-poly(ϵ-caprolactone) (poly(DA-CL)) added as a surface active agent. Propagation was initiated in the homogeneous systems. When propagating macromolecules reach their critical lengths ( M n ≈1000), they precipitate, and stabilized by macromolecules of poly(DA-CL) form nuclei of microspheres. The number of particles formed in the initial period of the pseudoanionic polymerization of l , l -lactide and ϵ-caprolactone remains constant whereas in the anionic polymerization of ϵ-caprolactone a weak aggregation, manifested by decreasing number of particles, was observed. Determination of partition of monomer and active centers between continuous and condensed (particles) phases revealed that polymeric particles were highly swollen with monomer (e.g. after incubation of poly(ϵ-caprolactone) latex ([poly(CL)]=2.17×101 g/l) in a solution containing initially [ϵ-caprolactone]=7.50×10−2 mol/l, 28% of monomer became incorporated into polymer particles) and that shortly after the initiation period all active centers were located inside growing latex particles. High local concentrations of monomer and active centers resulted in rates of polymerization which were up to ca 25 times higher than the rates of similar polymerization with the same monomer and initiator concentrations averaged over the whole volume of the reaction mixtures. Diameters of obtained poly(ϵ-caprolactone) latex particles were in the region from 0.6 to 0.7 μm and diameters of poly(lactide) microspheres varied from 2.2 to 4.2 μm depending on the polymerization conditions. Polydispersity of particle diameters was found to be strongly dependent on the ratio of molecular weight of poly(ϵ-caprolactone) grafts and molecular weight of poly(DA-CL) copolymer. The most uniform poly( l , l -lactide) microspheres (Dv/Dn 100 000, free from the admixture of cyclic oligomers and with Mw/Mn=1.06.

Polyglycidol, Its Derivatives, and Polyglycidol-Containing Copolymers—Synthesis and Medical Applications

Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a –CH2OH 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.

A novel electrochemically synthesized biodegradable thin film of polypyrrole–polyethyleneglycol–polylactic acid nanoparticles

Nanoparticles having reactive pyrrole residues were prepared from poly(1-ethoxyethylglycidyl ether)-block-poly(L,L-lactide) block copolymer. The nanoparticles were electropolymerized in aqueous media through the oxidation of the pyrrole residue and in the presence of pyrrole to form a nanocomposite thin film. The novel synthesis of these pyrrole-functionalized nanoparticles is described and the electrochemical deposition of the corresponding coating is characterized using electrochemistry, SEM and EDX.

Phase transfer and characterization of poly(ε-caprolactone) and poly(L-lactide) microspheres

A method suitable for transfer of poly(ε-caprolactone) and poly(L-lactide) microspheres (synthesized by pseudoanionic dispersion polymerization of ε-caprolactone and L-lactide in heptane1,4-dioxane mixed solvent) from heptane to water was developed. This method consists of treating the microspheres with KOH-ethanol in the presence of surfactants (nonionic Triton X-405, anionic sodium dodecyl sulfate (SDS), and zwitterionic ammonium sulfobetaine-2 (ASB)). Partial hydrolysis of polyesters results in the formation of hydroxyl and carboxyl groups in the surface layer of microspheres and enhances their stability in water-based media. Minimal concentrations of surfactants, needed to obtain stable suspensions of particles, were equal to 3 × 10-2, and 6 × 10-2, and 3 × 10-2 mol l-1 for Triton X-405, SDS, and ASB, respectively. In the case of poly(ε-caprolactone) microspheres, suspensions in water were stable for all three surfactants for pH values ranging from 3 to 11. Suspensions of poly(L-lactide) were stable in the same range of pH values only for ASB. Surface charge density determined by electrophoretic mobility varied for poly(ε-caprolactone) microspheres from 2.6 × 10-7 to 8.9 × 10-7 mol m-2, for particles stabilized with Triton X-405 and ASB, respectively. In the case of poly(L-lactide) microspheres, surface charge density varied from 3.9 × 10-7 (stabilizer: Triton X-405) to 7.4 × 10-7 mol m-2 (stabilizer: ASB). Carboxyl groups located in the surface layer of poly(L-lactide) microspheres were used for covalent immobilization of 6-aminoquinoline, a fluorophore with an amino group. Maximum surface concentration of immobilized 6-aminoquinoline was equal to 1.9 × 10-6 mol m-2. Poly(ε-caprolactone) microspheres transferred into water were loaded with ethyl salicylate. Loading up to 38% (w/w) was obtained.

Poly(L,L-lactide) and poly(L,L-lactide-co-glycolide) microparticles by dialysis

Abstract 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 (Dw̅/Dn̅ ) 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%.