Polylactic acids

Polylactic acid (PLA) is the second common biopolymer that is produced by microbial fermentation. It is thermoplastic aliphatic polyester that can be synthesized from biologically produced lactic acid polymerized by ring opening polymerization. Lactic acid is a chiral molecule existing as two stereoisomers, L- and D-lactic acid, which can be produced by different ways, i.e., biologically or chemically synthesized [Averous, 2008). 

Bacterial fermentation is used to produce lactic acid from corn starch or cane sugar which is further processed to produce lactide monomer. Because lactic acid is difficult to polymerize directly to high polymers in a single step on a commercial scale, most companies used a two-step process. Lactic acid is first oligomerized to a linear chain with a MW of less than 3,000 by removing water. 

The oligomer is then depolymerized to lactide, a cyclic dimer. 

PHA and PLA are both considered synthetic polymers, as they are not found in nature. However, they are wholly biodegradable [Kolybaba et al., 2001]. 

Biodegradable polymers, such as poly(L-lactic acid) (PLLA) and PLGA are suitable for drug-delivery applications due to their non-toxicity and adjustable biodegradability [25, 26]. PLGA and PLLA films have been used for the treatment of periodontal disease [27], glaucoma [28] and cancer [29], and as a component of biodegradable stents [30, 31]. 

Yingwei et al. [151] have investigated the rheological electrical and thermal properties of polylactic acid-organoclay nanocomposites. Both storage and loss modulus increased with clay loading at all frequencies. 

The virgin polylactic acid and its clay nanocomposites, upon foaming with carbon dioxide and nitrogen as a blowing agent, showed, in the case of the nanocomposites, a reduction in all sizes and an increase in cell density. 

In general, it was found that increasing the content of organically modified clays and montmorillonite increased the storage and loss module and the Young s modulns of poly vinylidene fluoride, and also reduced crystallinity and increased the 7. Also, the thermal stability tended to improve. 

The storage modulus of the reinforced polymer was improved appreciably over the storage modulus obtained for the virgin polymer over the temperature range -100°C to 150°C. 

Producing biobased monomers by fermentation/conventional chemistry followed by polymerization (e.g., polylactic acid, polybutylene succinate and polyethylene)  

Producing biobased polymers directly by bacteria (e.g., polyhydroxyalkanoates). 

Polylactic acid (PLA) has been known since 1845 but not commercialized xmtil early 1990. PLA belongs to the family of aliphatic polyesters with the basic constitutional unit of lactic acid. The monomer lactic acid is the hydroxyl carboxylic acid which can 

PLA is a biodegradable polymer used in tissue engineering for medical applications. Based on optical rotation, PLA materials include the dextrorotatory (D) and dextro, levo rotatory (D,L) forms. The properties of PLA are given in Table 2.6. The structures of the different forms are identical, but they differ in their crystallinity. PLA (D) has a crystalline structure and is tough, with melting temperature = 180 °C and glass transition temperature Tg = 67 °C, whereas PLA (D,L) has an amorphous structure (with toughness) and Tg = 57 °C [30]. 

PLA plays an important role among synthetic biodegradable polyesters, thanks to its low price. Moreover, it is made from 100% renewable resources (Section 10.4), which is an aspect becoming more and more important. 

PLA is synthesised by the ring-opening polymerisation of lactide [10, 11, 24], the cyclic dimer of lactic acid, which is produced on a large scale via fermentation. 

Properties of PLA are highly related to the ratio between the two optical isomers, D and L. 

With regards to PLA on the market, it is usually a copolymer of L-lactide containing 2-4% of D-lactide along its polymer chain. This causes a decrease in the melting temperature (Tm) which can drop from nearly 180-190 °C for pure poly(L-lactic acid) to 140-150 °C for PLA containing almost 4% of D-lactide in the polymer chain [25, 26]. PLA is a rigid and stiff product with a Tg of 60-65 C. 

There are many other companies which produce PLA, amongst them Mitsui (LACEA PLA), Futerro, which is a joint venture between Galactic and Total (Futerro PLA), Dainippon Ink Chemicals Inc (CPLA PLA), Purac and Zhejiang Hisun. 

There are several promising markets for biodegradable polymers such as polylactide. Plastic bags for household bio waste, barriers for sanitary products and nappies (diapers), planting cups, disposable cups and plates are some typical applications. To date no commercial large-scale production of polylactide exists, but this is likely to change in the near future. 

The starting material, lactic acid, will also need new capacity. Commercial markets for biodegradable polymers are expected to increase substantially in the coming years. 

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Polylactic Acid. Polylactic acid (PLA) was introduced in 1966 for degradable surgical implants. Hydrolysis yields lactic acid, a normal intermediate of carbohydrate metaboHsm (23). PolyglycoHc acid sutures have a predictable degradation rate which coincides with the healing sequence of natural tissues. 

Polylactic acid, also known as polylactide, is prepared from the cycHc diester of lactic acid (lactide) by ring-opening addition polymerization, as shown below ... 

Similar to pure polyglycoHc acid and pure polylactic acid, the 90 10 glycolide lactide copolymer is also weakened by gamma irradiation. The normal in vivo absorption time of about 70 days for fibrous material can be decreased to less than about 28 days by simple exposure to gamma radiation in excess of 50 kGy (5 Mrads) (35). 

Braided Synthetic Absorbable Sutures. Suture manufacturers have searched for many years to find a synthetic alternative to surgical gut. The first successful attempt to make a synthetic absorbable suture was the invention of polylactic acid [26023-30-3] suture (15). The polymer was made by the ring-opening polymerization of L-lactide [95-96-5] (1), the cycUc dimer of L-lactic acid. 

Polylactic acid sutures are slowly degraded by the foUowing hydrolysis reaction shown and can take years to be completely absorbed (16). These sutures were never commercialized. 

In 1967, a polyglycoUc acid [26124-68-5] suture (17) made by the ring-opening polymerization of glycoUde (2), the cycUc dimer of glycoUc acid, was invented. PolyglycoUc acid sutures are degraded by hydrolysis more rapidly than polylactic acid. 

It is essential to neutralize any strong acid present before distilling lactic esters otherwise, condensation by ester interchange occurs, with liberation of alcohol and production of polylactic acid, a linear polyester. Other neutralizing agents, such as alkali or alkaline-earth hydroxides or carbonates, doubtless could be used satisfactorily instead of sodium acetate. 

Bio-based materials are materials that are taken from or made from natural materials in living things. Examples include packing pellets made from corn and soybeans, polylactic acid (a polymer used to make plastic packaging), and various kinds of pharmaceuticals. 

A number of articles considered the association of chitosan with polylactic acid or similar compounds [47-49] another group of articles presented new data on highly cationic chitosans [ 50 - 55]. More data have also been made available on the delivery of growth factors [56] and ophthalmic drugs [57,58], on the activation of the complement, macrophages [59-61] and fibroblasts [62], on mucoadhesion [63] and functionalization of chitin [64]. The development of new carriers for the delivery of drugs, and the interactions of chitosans with living tissues seem therefore to be major topics in the current research on chitosan. Therefore, this chapter will place emphasis on these aspects. 

Al-Mulla, E.A.J., Yimus, W.MZ., Ibrahim, N.A. and Abdul Rahman MZ. 2010b. Properties of epoxidized palm oil plasticized polylactic acid. Journal of Materisls Science 45 ... 

Al-Mulla, E.A.J. 2011. Polylactic acid/epoxidized palm oil/fatty nitrogen compounds modified clay nanocomposites Preparation and characterization. Korean Journal of... 

Drumright, R.E., Gruber, P.R and Henton, D.E. 2000. Polylactic acid technology. Advanced Materials 12 1841-6. 

Sinclair, R.G. 1996. The case for polylactic acid as a commodity packaging plastic. Journal of Macromolecular Science Pure and Applied Chemistry 33 585-97. 

G. C., Resorption rate, route of elimination, and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat, J. Biomed. Mater. Res., 7, 155, 1973. 

Brekke, J. H., Bresner, M., and Reitman, M. J., Polylactic acid surgical dressing material. Postoperative therapy for dental extraction wounds. Can. Dent. Assoc. J., 52, 599,... 

A method of the preparation of polylactic acid microcapsules of controlled particle size and drug loading, J. Microencapsul.,... 

J. B., Polylactic acid as a biodegradable carrier for contraceptive steroids. Contraception, 8, 227, 1973. 

Juni, K., Ogata, J., Nakano, M., Ichihara, T., Mori, K., and Akagi, M., Preparation and evaluation in vitro and in vivo of polylactic acid microspheres containing doxorubicin, Chem. Pharm. Bull.. 33, 313, 1985. 

M., Modification of the release rate of aclarubicin from polylactic acid microspheres by using additives, Chem. Pharm. 

Lin, S. Y., Ho, L. T., Chiou, H. L., Microencapsulation and controlled release of insulin from polylactic acid microcapsules. Biomater. Med. Devices Artif. Organs. 86, 187, 1985. 

FIGURE 5 Stepwise synthesis of a triblock copolymer (PCL-PLA-PCL) of PCL and polylactic acid using aluminum coordination catalysts to minimize randomization of the block structure by transesterification. (From Ref. 43.)... 

Polymer blends have been categorized as (1) compatible, exhibiting only a single Tg, (2) mechanically compatible, exhibiting the Tg values of each component but with superior mechanical properties, and (3) incompatible, exhibiting the unenhanced properties of phase-separated materials (8). Based on the mechanical properties, it has been suggested that PCL-cellulose acetate butyrate blends are compatible (8). Dynamic mechanical measurements of the Tg of PCL-polylactic acid blends indicate that the compatability may depend on the ratios employed (65). Both of these blends have been used to control the permeability of delivery systems (vide infra). 

FIGURE 12 Control of the rate of release of methadone from microspheres by the use of blends of a e-caprolactone-lactic acid copolymer and polylactic acid. (From Ref. 63.)... 

Whereas conventional poly (amino acids) are probably best grouped together with proteins, polysaccharides, and other endogenous polymeric materials, the pseudopoly (amino acids) can no longer be regarded as "natural polymers." Rather, they are synthetic polymers derived from natural metabolites (e.g., a-L-amino acids) as monomers. In this sense, pseudopoly (amino acids) are similar to polylactic acid, which is also a synthetic polymer, derived exclusively from a natural metabolite. 

Polylactic acid (PLA) has been produced for many years as a high-value material for use in medical applications such as dissolvable stitches and controlled release devices, because of the high production costs. The very low toxicity and biodegradability within the body made PLA the polymer of choice for such applications. In theory PLA should be relatively simple to produce by simple condensation polymerization of lactic acid. Unfortunately, in practice, a competing depolymerization process takes place to produce the cyclic lactide (Scheme 6.10). As the degree of polymerization increases the rate slows down until the rates of depolymerization and polymerization are the same. This equilibrium is achieved before commercially useful molecular weights of PLA have been formed. 

Polylactic acid Polyglycolic acid Polycaprolactone Polyhydroxybutyrate Polyhydroxyvalerate... 

HJ Krause, A Schwarz, P Rohdewald. Polylactic acid nanoparticles, a colloidal drug delivery system for lipophilic drugs. Int J Pharm 27 145-155, 1985. 

DL-polylactic acid 25-75 Subcutaneous delivery of local anesthetics Dibucaine tetracaine... 

In addition to solvent uses, esters of lactic acid can be used to recover pure lactic acid via hydrolysis, which in-tum is used to make optically active dilactide and subsequently polylactic acid used for drag delivery system.5 This method of recovery for certain lactic acid applications is critical in synthesis of medicinal grade polymer because only optically active polymers with low Tg are useful for drug delivery systems. Lactic acid esters themselves can also be directly converted into polymers, (Figure 1), although the commercial route proceeds via ring-opening polymerization of dilactide. 

Hartmann, M.H. (1998). High molecular weight polylactic acid polymers. In Kaplan, D.L., editor. Biopolymers from Renewable Resources. Springer, Berlin. 

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