Poly(isoglycerol methacrylate)-b-poly(d or l-lactide) Copolymers: A Novel Hydrophilic Methacrylate as Building Block for Supramolecular Aggregates

On the basis of a new acetal-protected glycerol monomethacrylate monomer (cis-1,3-benzylidene glycerol methacrylate/BGMA) a series of potentially biocompatible and partially biodegradable homo- and block copolymers were synthesized. ATRP polymerization of BGMA yielded well-defined polyacrylates with pendant benzylidene acetal groups and high glass transition temperatures (115−130 °C). This hydrophobic poly(cis-1,3-benzylidene glycerol methacrylate) could be readily transformed into the hydrophilic and water-soluble poly(1,3-dihydroxypropyl methacrylate), referred to as poly(isoglycerol methacrylate) (PIGMA). It exclusively contains primary hydroxyl groups and therefore differs significantly…

P(HPMA)-block-P(LA) copolymers in paclitaxel formulations: Polylactide stereochemistry controls micellization, cellular uptake kinetics, intracellular localization and drug efficiency

In order to explore the influence of polymer microstructure and stereochemistry in biological settings, the synthesis, micellization, cellular fate and the use in paclitaxel formulations of poly(N-(2-hydroxypropyl)-methacrylamide)-block-poly(L-lactide) (P(HPMA)-block-P(LLA)) and poly(N-(2-hydroxypropyl)-methacrylamide)-block-poly(DL-lactide) block copolymers (P(HPMA)-block-P(DLLA)) were studied. To this end, P(HPMA)-block-P(lactide) block copolymers and their fluorescently labeled analogues were synthesized. The polymers exhibited molecular weights M-n around 20,000 g/mol with dispersities (D=M-w/M-n) below 1.3. In addition, the solution conformation of this new type of partially degradable…

Oligo(glycerol) Methacrylate Macromonomers

Linear, protected ω-methoxy oligo(glycerol) methacrylate (OGly(P)MA) macromonomers are synthesized via anionic ring-opening polymerization of ethoxyethyl glycidyl ether (EEGE) followed by termination with methacrylic acid anhydride (DP(n) = 3-11, PDI < 1.30). The covalently bound methacrylate moiety allows the homopolymerization of OGly(P)MA as well as copolymerization with low molecular weight comonomers. In homopolymerizations, macromonomers are polymerized by atom transfer radical polymerization (ATRP) yielding well-defined graft polymers (M(n) = 20,000-30,000 g mol(-1)). Acidic hydrolysis of the protecting groups releases water-soluble polyhydroxy-functional structures. First results on…

Synthesis, Characterization and Preliminary Biological Evaluation of P(HPMA)-b-P(LLA) Copolymers: A New Type of Functional Biocompatible Block Copolymer

We describe a synthetic pathway to functional P(HPMA)-b-P(LLA) block copolymers. The synthesis relies on a combination of ring-opening polymerization of L-lactide, conversion into a chain transfer agent (CTA) for the RAFT polymerization of pentafluorophenyl methacrylate. A series of block copolymers was prepared that exhibited molecular weights $\overline M _{\rm n}$ ranging from 7 600 to 34 300 g · mol(-1) , with moderate PDI between 1.3 and 1.45. These reactive precursor polymers have been transformed into biocompatible P(HPMA)-b-P(LLA) copolymers and their fluorescently labeled derivatives by facile replacement of the pentafluorophenyl groups. The fluorescence label attached to this new …

Long-Chain Branched Poly(Lactide)s Based on Polycondensation of AB2 -type Macromonomers

A series of long-chain branched poly(d-/l-lactide)s is synthesized in a two-step protocol by (1) ring-opening polymerization of lactide and (2) subsequent condensation of the preformed AB2 macromonomers promoted by different coupling reagents. The linear AB2 macromonomers are prepared by Sn(Oct)2-catalyzed ROP of D- and L-lactide with 2,2-bis(hydroxymethyl)butyric acid (BHB) as an initiator. Optimization of the polymerization conditions allows for the preparation of well-defined macromonomers (Mw/Mn = 1.09–1.30) with adjustable molecular weights (760–7200 g mol−1). The two-step approach of the synthesis comprises as well the coupling of these AB2 macromonomers and hence allows precise contr…

Macromol. Rapid Commun. 17/2010

Inimer-Promoted Synthesis of Branched and Hyperbranched Polylactide Copolymers

A series of (hyper)branched poly(l-lactide)(PLLA) copolymers has been prepared by ring-opening multibranching copolymerization of l-lactide with a hydroxyl-functional (ABB′) lactone inimer, 5HDON (5-hydroxymethyl-1,4-dioxane-2-on). Polymerization was conducted in bulk and solution and catalyzed either by stanneous-2-ethyl hexanoate (Sn(Oct)2) or an organic base, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Precise structural characterization of the resulting branched copolyester structures was accomplished by a combination of 2D NMR techniques, relying on the comparison with model compounds. The 5HDON inimer was employed in 1% to 20% fractions and is incorporated either as a dendritic unit or…

Poly(glycolide) multi-arm star polymers: Improved solubility via limited arm length.

Due to the low solubility of poly(glycolic acid) (PGA), its use is generally limited to the synthesis of random copolyesters with other hydroxy acids, such as lactic acid, or to applications that permit direct processing from the polymer melt. Insolubility is generally observed for PGA when the degree of polymerization exceeds 20. Here we present a strategy that allows the preparation of PGA-based multi-arm structures which significantly exceed the molecular weight of processable oligomeric linear PGA (&lt;1000 g/mol). This was achieved by the use of a multifunctional hyperbranched polyglycerol (PG) macroinitiator and the tin(II)-2-ethylhexanoate catalyzed ring-opening polymerization of gly…

Multi-Arm Star Poly(L-lactide) with Hyperbranched Polyglycerol Core

Biocompatible multi-arm star block copolymers based on poly(L-lactide) (PLLA) have been prepared by a core-first approach, using hyperbranched polyglycerol (PG), a polyether polyol, as a polyfunctional initiator. The molecular weight of the hyperbranched initiator-core was varied from 2 200 to 5 200 g mol -1 , molecular weights of the resulting multi-arm stars were in the range of 6 700-107 000 g mol -1 (NMR), depending on the amount of dilactide (LA) added. Various monomer/initiator ratios have been employed in the Sn-catalyzed LA polymerization in order to vary the length of the lactide arms from DP n (arm) = 2 to 20 units. Detailed NMR analysis using conventional and 2D-NMR techniques (e…