PLA, PGA, and PLGA as biomaterials

Background

The polymer materials of polylactic acid (PLA), polyglycolic acid (PGA), and poly(lactic-co-glycolic) acid (PLGA) have been shown in recent years to be strong contributors to the development of biodegradable medical implants within the human body, drug carrier designs, and even uses in the packaging industry. The immense utility of many of these polymers were over looked due to their degradation via hydrolysis. The increase in popularity can be attributed to a general increase in demand for biodegradable plastics (Xiao et al.). More focus on environmental responsibility as well as a push away from plastics produced from fossil fuel sources, create a high demand for plastics that are both biodegradable and able to be produced from organic sources (Cheng et al.) (Xiao et al. Fig 1).

There are three main areas of use for PLA, PGA, and PLGA plastics: (1) Use a drug carrier in drug delivery applications (2) The promotion of cell growth and organ healing in cell scaffolds and other tissue engineered materials (3) The implementation of plastics in packaging materials (Cheng et al.; Xiao et al.). It is also advantageous to utilize co-polymer and polymer blends of biodegradable monomers of PLA and PGA. PLGA is the most obvious example of Lactic Acid and Glycolic Acid co-polymerization. Some other common monomers that a co-polymerized with these monomers are malic acid or PEG (Cheng et al.). Some of the properties that can be modified through blending and co-polymerizing these polymers are biodegradability, hydrophilicity, mechanical properties, physical properties, and surface topography (Lee et al.; Sasatsu et al.).

History

1780 - Lactic Acid first discovered in 1780 by Carl Wilhelm Scheele (Experimental Chemist) (Auras et al.)

1880s - Industrial production of Lactic Acid in US (Auras et al.)

1944 - Study of Lactic Acid Condensation Polymers (Filachione et al.)

1954 - PGA became known (Gilding et al.)

1962 - PGA suture marketed as Dexon (Gilding et al.)

1994 - Kanebo LTd. introduced Lactron PLLA fiber adn spun-laid nonwovens (Auras et al.).

1996 - Mitsui Chemicals, Inc. commercialized PLA produced by polycondensation route (Auras et al.).

1997 - Formatin of Cargill Dow LLC, to commercialize PLA under the name NatureWorks (Auras et al.).

2003 - Toyota produced PLA for automotive applications (Auras et al.).

2005 - NatureWorksLLC and Teijin Limited formed 50-50 joint venture to market Ingeo bio-based thermoplastic resins (Auras et al.).

2008 - PURAC started to commercialize solid lactide monomers under PURALACT (Auras et al.).

2009 - PURAC, Sulzer, and Synbra announced production of PLA from solid lactide for foamed products (Auras et al.).

2010 - Recombinant Escherichia coli to produce PLA (Auras et al.).

Synthesis

The synthesis PLA, PGA, and PLGA can be done under many different mechanisms with main mechanisms being (1) Direct condensation polymerization (2) Ring Opening Polymerization each with its own set of advantages and disadvantages.

Polylactic Acid and Polyglycolic Acid

The extraction of the monomers is often not conducted by synthetic means unlike conventional plastics. Currently, most Lactic acid is produced through a fermentation process, over a synthetic method (Auras et al.).

Bio-degradation Mechanism

Being aliphatic polyesters PLA, PGA, and PLGA are flexible and all degrade at certain pH range. This degradation is conducted via hydrolic cleavage of the bond between monomers (Auras et al.).

Sources

Auras, R.; Lim L.; Selke, S. E. M.; Tsuji, H. Poly(Lactic Acid): Synthesis, Structures, Properties, Processing, and Applications; John Wiley & Sons: [Online], 2010.

Cheng, Y.; Deng, S.; Chen, P.; Ruan, R. Polylactic acid (PLA) synthesis and modification: a review. Front. Chem. China. 2009, 4(3). pp. 259-264

Filachione, E. M.; Fisher, C. H., Lactic Acid Condensation Polymers. Ind.. Eng. Chem. 1944, 36, 223.

Gilding, D. K.; A. M. Reed. Biodegradable polymers for use in surgery - polyglycolic/poly (lactic acid) homo- and copolymers: 1. Polymer. 1979. 20 (12): 1459–1464.

Gupta, B.; Revagade, N.; Hilborn J. Poly(lactic acid) fiber: An overview. Prog. Polym. Sci. 2007, 32. 455-482.

Kowalski, A.; Duda, A.; Penczek, S.,Kinetics and mechanism of cyclic esters polymerization initiated with tin(II) octoate, 1. Polymerization of ε-caprolactone. Macromol. Rapid Commun. 1998, 19, 567

Lee, S. G.; An, E. Y.; Lee, J. B.; Park, J. C.; Shin, J. W.; Kim, G. K., Enhanced cell affinity of poly(d,l-lactic-co-glycolic acid) (50/50) by plasma treatment with β-(1 → 3) (1 → 6)-glucan. Surf. Coat. Technol. 2007, 201, 5128.

Luu, Y.K.; Kim, K.; Hsiao, B.S.; Chu, B.; Hadjiargyrou, M. Development of a nanosructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers. Journal of Controlled Release.2003, 89, pp. 341-353.

Majerska, K.; Duda, A.; Penczek, S.,Kinetics and mechanism of cyclic esters polymerisation initiated with tin(II) octoate, 4. Influence of proton trapping agents on the kinetics of ε-caprolactone and L,L-dilactide polymerisation. Macromol. Rapid Commun. 2000, 21, 1327

Sasatsu, M.; Onishi, H.; Machida, Y.,In vitro and in vivo characterization of nanoparticles made of MeO-PEG amine/PLA block copolymer and PLA. Int. J. Pharm. 2006, 317, 167.

Xiao, L.; Wang, B.; Yang, G.; Gauthier, M. Poly(Lactic Acid)-Based Biomaterials: Synthesis, Modification and Applications. Biomedical Science, Engineering and Technology. 2012, pp. 247-282.