Monday, February 22, 2016

Poly(lactide-co-glycolide) degradation rate relationship with surface area to volume

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polyesters including PLGA and others. These polyesters hydrolyze based on random chain scissions along the ester backbone which cut the polymer into smaller components down until they are returned to their original lactic acid and glycolic acid monomeric units. Because of this non-toxic biodegradation, PLGA is widely used for drug delivery and implant applications. One question remains: how long does this process take to occur? This is truly a multi-faceted and complex question relating to the type of PLGA used and its formulation properties. The key parameters which affect this are water access and reactivity. At neutral pH, the hydrolysis reaction is fairly slow but it is accelerated at low pH as well as at high pH. Additionally, the hydrophobic polymer chain itself and polymer characteristics such as crystallinity can act to sterically hinder water access which slows down the degradation rate. Recently, researchers at University of Texas investigated the effect of surface-area-to-volume ratio for PLGA degradation by making scaffolds at varying SVR (some which were very thick and others which were thin). They found, in this situation, that the buildup of low-pH acidic components contributed more significantly to the degradation rate than the restricted water access of the thicker polymer pieces. This is useful in understanding that thicker drug delivery systems are not always slower despite their reduced SVR. Read more about their research here: Chew, Sue Anne, Marco Arriaga, and Victor Hinojosa. "Effects of surface area to volume ratio of plga scaffolds with different architectures on scaffold degradation characteristics and drug release kinetics." Journal of Biomedical Materials Research Part A (2016). http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.35657/abstract

“Abstract: In this work, PLGA scaffolds with different architectures were fabricated to investigate the effects of surface area to volume ratio (SVR) (which resulted from the different architectures) on scaffold degradation characteristics and drug release kinetics with minocycline as the model drug. It was hypothesized that the thin strand scaffolds, which had the highest SVR, would degrade faster than the thick strand and globular scaffolds as the increase in surface area will allow more contact between water molecules and degradable ester groups in the polymer. However, it was found that globular scaffolds, which had the lowest SVR, resulted in the fastest degradation which demonstrated that the amount of degradation of the scaffolds does not only depend on the SVR but also on other factors such as the retention of acidic degradation byproducts in the scaffold and scaffold porosity. PLGA 50 : 50 globular scaffolds resulted in a biphasic release profile, with a burst release in the beginning and the middle of the release study which may be beneficial for some drug delivery applications. A clear correlation between SVR and release rates was not observed, indicating that besides the availability of more surface area for drug to diffuse out of the polymer matrix, other factors such as amount of scaffold degradation and scaffold porosity may play a role in determining drug release kinetics. Further studies, such as scanning electron microscopy, need to be performed in the future to further evaluate the porosity, morphology and structure of the scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2016. Keywords: PLGA scaffolds;surface area to volume ratio;scaffold architecture;degradation characteristics;drug release kinetics”
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