Low-molecular-weight PLA

Figure 9.2. Lactide ring formation by depolymerization of low-molecular weight PLA. Reprinted with permission from J. Lunt, Polymer Degradation and Stability, Vol. 59, p. 145,1998, 1998, Elsevier Science Ltd.

Polylactic acid was first discovered in the 1930s when a DuPont scientist, Wallace Caruthers, produced a low molecular weight PLA product. In 1954, DuPont patented Carothers process. Initially the focus was on the manufacture of medical grade applications due to the high cost of the polymer, but advances in fermentation of glucose, which forms lactic acid, has dramatically lowered the cost of producing lactic acid and significantly increased interest in the polymer. 

JEV-loaded poly(lactide) (PLA) lamellar and PLG microspheres were successfully prepared with low-molecular-weight PLA by the precipitate method and with 6% w/v PLG in the organic phase, 10% w/v PVP, and 5% w/v NaCl in the continuous phase by using a w/o/w emulsion/solvent extraction technique, respectively [233], The JEV incorporation, physicochemical characterization data, and animal results obtained in this study may be relevant in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers. 

Biodegradable polymer blends of polyanhydrides and polyesters have been used as drug carriers [59], Polyflactic acid) (PLA), polyfhydroxybutyrate) (PHB), and poly(caprolactone) (PCL), of 2000 and 50000 molecular weights were mixed with poly(sebacic anhydride) (PSA), and the properties of these mixtures were studied. Mixtures of PHB and low molecular weight PLA or PCL formed uniform blends with various amounts of PSA. These blends possess different physical and mechanical properties compared to the parent polymers. The release rate of drugs from these polymeric blends increases with the increase in the content of the rapidly degrading component, PSA. 

PolyQactic acid] was discovered by Carothers at DuPont in 1932. Only a low-molecular-weight PLA could be produced by heating lactic acid under vacuum while removing the condensed water [1]. 

Albertsson, 1999). In general, polyanhydrides of different structures form uniform blends with a single melting temperature. Low molecular weight PLA, PHB, and pol-y(caprolactone) (PCL) are miscible with polyanhydrides, while high molecular weight polyesters M > 10,000) are not compatible with poly anhydrides. 

Codari F, Moscatelli D, Storti G, Morbidelli M. Characterization of low-molecular-weight PLA using HPLC. Macromol Mater Eng 2010 295(1) 58—66. 

Based on this lactide intermediate method. Nature Works LLC has developed a patented, low cost continuous process for the production of lactic acid-based polymers. The process combines the substantial environmental and economic benefits of synthesizing both lactide and PLA in the melt rather than in solution and, for the first time, provides a commercially viable compostable commodity polymer made from annually renewable resources. The process starts with a continuous condensation reaction of aqueous lactic acid to produce low molecular weight PLA pre-polymer (Fig. 6.5). 

As mentioned above, the basic building block for PLA is lactic acid, which exists in two optically active configurations L(+) lactic acid and D(-) lactic acid. Another intermediate monomer for PLA synthesis is a lactide and obtained by the depolymerization of low molecular weight PLA under reduced pressure to give a mixture of L-lactide, D-lactide, or meso-lactide as shown in Figure 13. 

The water solubiUty of PLA-PEG and PLGA-PEG copolymers depends on the molecular weight of the hydrophobic (PLGA-PEG) and hydrophilic (PEG) blocks. Water soluble PLA-PEG copolymers with relatively low molecular weight PLA blocks self-disperse in water to form block copolymer micelles. For example, water soluble PLA-PEG 2 5 (M of PLA 2000 Da and M of PEG is 5000 Dalton) form spherical micelles 25 run in diameter. These micelles solubilize model and anticancer drugs by micellar incorporation. However, in vivo, the systemic lifetimes produced were relatively short and the clearance rate was signihcantly faster when the micelles are administered at low concentration. This suggests micellar dissociation at concentrations below the cmc. 

First, random chain scission of the ester groups of PLA reduces its molecular weight. The speed of chain scission depends on the pH value, temperature, and moisture levels of the environment [66]. Embrittlement of the polymers occurs with the reduction of its molecular weight. Second, low-molecular-weight PLA is metabolized by microorganisms, yielding carbon dioxide, water, and humus [67]. 

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