VALEROLACTONE COPOLYMER

Lee H, Zeng F, Dunne M, Allen C (2005) Metlioxy poly(etliylene glycol)-block-poly(delta-valerolactone) copolymer micelles for formulation of hydrophobic drugs. Biomacromolecules 6 3119-3128. 

Glycolide L-lactide copolymers Lactide trimethylene carbonate copolymers Lactide tetramethylglycolide copolymers Lactide a-valerolactone copolymers Methacrylate N-vinyl-pyrrolidone copolymers Lactic acid ethylene oxide copolymers... 

The mechanisms of biodegradation of polylactide, polycaprolactone and caprolactone copolymers with dilactide copolymer, valerolactone copolymer, and decalactone copolymer in the rabbit were shown to be qualitatively similar. The rate of the first stage of the degradation process, non enzymatic random hydrolytic chain scission, was found to vary by an order of magnitude and was dependent on morphological as well as chemical effects. 17 refs. 

Stannous octoate has the advantage of having been used to prepare polymers (Silastic, Capronor) for which substantial toxicological data are now available (6,48). Stannous octoate-initiated polymerization has been used to prepare copolymers of e-caprolactone with other lactones, including diglycolide, dilactide, 6-valerolactone, e-decalactone, and other alkyl-substituted e-caprolactones. Conducting... 

II. B polyethylene glycol, ethylene oxide, polystyrene, diisocyanates (urethanes), polyvinylchloride, chloroprene, THF, diglycolide, dilac-tide, <5-valerolactone, substituted e-caprolactones, 4-vinyl anisole, styrene, methyl methacrylate, and vinyl acetate. In addition to these species, many copolymers have been prepared from oligomers of PCL. In particular, a variety of polyester-urethanes have been synthesized from hydroxy-terminated PCL, some of which have achieved commercial status (9). Graft copolymers with acrylic acid, acrylonitrile, and styrene have been prepared using PCL as the backbone polymer (60). 

More definitive evidence of enzymatic attack was obtained with 1 1 copolymers of e-caprolactone and 6-valerolactone crosslinked with varying amounts of a dilactone (98,99). The use of a 1 1 mixture of comonomers suppressed crystallization and, together with the crosslinks, resulted in a low-modulus elastomer. Under in vitro conditions, random hydrolytic chain cleavage, measured by the change in tensile properties, occurred throughout the bulk of the samples at a rate comparable to that experienced by the other polyesters no weight loss was observed. However, when these elastomers were implanted in rabbits, the bulk hydrolytic process was accompanied by very rapid surface erosion. Weight loss was continuous, confined to the... 

FIGURE 23 Rate of enzymatic surface erosion of a 1 1 copolymer of e-caprolactone and 6-valerolactone, crosslinked with a dilactone to form an elastomer. The effect of substitution of the e-caprolactone nucleus is also shown. (From Ref. 98). 

Yasuda et al. [122] extended the above work to the block copolymerization of ethylene with lactones. 5-Valerolactone and s-caprolactone were combined with the growing polyethylene end at ambient temperature and the expected AB-type copolymers (100 1 to 100 89) were obtained at high yield. Reversed addition of the monomers (first MMA or lactones and then ethylene) induced no block copolymerization at all, even in the presence of excess ethylene, and only homo-poly(MMA) and homo-poly(lactone) were produced. 

Besides the investigation of stereoisomers, the degradation of copolymers with E-caprolactone [24, 28, 29], 5-valerolactone [24, 28, 29], y-butyrolacton [30] and D,L-lactide [31] were also studied. The trends are found to be independent of the co-monomer. Co-monomer units within the polymer lead to an increase of degradation rate up to ten times that of natural PHB. The reason for this finding is the change of crystallinity within in the synthetic material, which could by proved by various DSC measurements of different copolymers and compositions. 

Lou X, Detrembleur C, Jerome R (2002) Living cationic polymerization of 5-valerolactone and synthesis of high molecular weight homopolymer and asymmetric telechelic and block copolymer. Macromolecules 35 1190-1195... 

Zeng F, Lee H, Chidiac M, Allen C (2005) Synthesis and characterization of six-arm star poly (5-valerolactone)-Woci -methoxy poly(ethylene glycol) copolymers. Biomacromolecules 6 2140-2149... 

BMM623>, /3-valerolactone <2002JA15239>, and a-methyl-/3-pentylpropiolactone <2004T7177>. The polyester formed from the latter monomer was used in the formulation of immiscible blends or block copolymers with the biodegradable aliphatic polyester polylactide <2004T7177>. 

Poly(e-caprolactone) (PCL) is synthesized by anionic, cationic or coordination polymerization of e-caprolactone. Degradable block copolymers with polyethylene glycol, diglycolide, substituted caprolactones and /-valerolactone can also be synthesized. Like the lactide polymers, PCL and its copolymers degrade both in vitro and in vivo by bulk hydrolysis, with the degradation rate affected by the size and shape of the device and additives. 

We have extended the above work to the block copolymerization of ethylene with lactones. 6-Valerolactone and e-caprolactone were incorporated to the growing polyethylene end at ambient temperature and the expected AB type copolymers (100 1 to 100 89) were obtained in high yield. 

Higher molecular weight PHB and its copolymers with poly(3-hydroxy-valerate) (PHV) can be synthesized from racemic P-butyrolactone and P Valerolactone, using an oligomeric alumoxane catalyst. These polyesters, with only partial stereoregularity, are less susceptible to enzymatic degradation than the bacterial ones. Polyhydroxy-butyrate-valerate (PHBV) is produced by Monsanto as Biopol . 

More recently, Lopez-Luna et al. [54] reported the successful enzyme-mediated syntheses of polyester structures in SCCO2 and R-134a. Lipase-mediated synthesis of relatively high molecular weight poly(S-valerolactone) (PVL) was reported in SCCO2 and liquid R-134a solvent media. However, they found that polymers and copolymers... 

Pratt et al. reported the synthesis of a series of lactide containing block copolymers using monohydroxy-functional macroinitiators and a thiourea/(—)-sparteine catalyst [41], In another publication from the same group around Hedrick the synthesis of lactide, valerolactone, and caprolactone from monohydroxy-functional PS-OH, PEO-OH and PDMA-OH using TBD as catalyst was demonstrated [40]. 

Most microbially produced polymers are known to be stiff and not very flexible. However, one potential microbially derived polymer that is more supple is a lactic acid-P-methyl-5-valerolactone( M5VL)-lactic acid triblock copolymer. This was demonstrated by the overproduction of mevalonate in E. coli via enzymes from L. casei which generate mevalonate, a precursor of the isoprenoid pathway, from acetyl-CoA. Mevalonate is produced at over 80gl from glucose, dehydrated, and then reduced to form M WL. PLA-PPM5VL-PLA triblock copolymers were created to demonstrate physical properties such as elasticity and toughness [141]. 

Cationic copolymers in the form of nanoparticles were also used to increase water solubility of water-insoluble drugs. This is an important application since one-third of newly discovered drugs are only sparingly soluble in water. Copolymers of 5-Z-amino-8-valerolactone and s-caprolactone were... 

The successful examples of transformation involving polarity inversion were reported by Endo et al. for the preparation of block copolymers of THF with tert-butyl methacrylate (tBMA), s-caprolactone (CL), 8-valerolactone (VL), tBA, and MMA as shown in Scheme 25. 

The kinetics of the free radical emulsion polymerization of a-meth-ylene-y-valerolactone has been investigated (58). Stable polymer latices could be prepared. A homogeneous nucleation is the dominant path for particle formation. Also, the miniemulsion copolymerization with styrene as comonomer has been investigated. Both the reversible addition-fragmentation chain transfer (RAFT) miniemulsion polymerization and the RAFT bulk polymerization are weU controlled and copolymers with a narrow polydispersity are formed. 

Zhu and Lei reported that the neutral degradation rate of poly(DLLA-co-adipic anhydride) increased at higher content of adipic anhydride. Nakayama et reported that the addition of 20 mol% of p-methyl-valerolactone (VL) considerably increased the degradation rate of P(LLA-co-p-methyl-VL) copolymers. However, high contents of 8-valerolactone units in PLLA copolymers were found to decrease the hydrolytic degradation rate in neutral media. 

Synthesis of Copolymers of Lactic Acid 6-Valerolactone and Lactic Acid 3-Butyrolactone... 

Very few studies have been reported on the copolymerization of LA with 6-valerolactone (VL) and 3-butyrolactone (BL). Anionic block copolymerization of VL and LLA in the presence of potassium methoxide in THE at 20°C gave diblock copolymers with expected compositions and molecular weights [44]. Slight racemization of LLA was observed during polymerization due to transesterification reactions. 

A series of papers has been published on the direct degradation of a variety of polyesters in the ion source of a mass spectrometer. Polymers examined were poly(/3-propiolactone), poly(/S-pivalolactone), poly(y-valerolactone) poly-lactide, polyglycolide, and a glycolic acid-lactic acid copolymer poly(oxysuc-cinyloxy-1,4-phenylene) and poly(oxyterephthaloyloxy-l,4-phenylene). ... 

---