Abstract
Poly(lactic-co-glycolic acid) (PLGA) is among the most common of biodegradable polymers studied in various biomedical applications such as drug delivery and tissue engineering. To facilitate the understanding of the often overlooked impact of PLGA microstructure on important factors affecting PLGA performance, we measured four key parameters of 17 commonly used commercial PLGA polymers (Expansorb®, Resomer®, Purasorb®, Lactel®, and Wako®) by NMR spectroscopy. 1HNMR and 13CNMR spectra were used to determine lactic to glycolic ratio (L/G ratio), polymer end-capping, glycolic blockiness (Rc), and average glycolic and lactic block lengths (LG and LL). In PLGAs with a labeled L/G ratio of 50/50 and acid end-capping, the actual lactic content slightly decreased as molecular weight increased in bothExpansorb® and Resomer®. Whether or not acid- or ester-, termination of these PLGAs was confirmed to be consistent with their brand labels. Moreover, in the ester end-capped 75/25 L/G ratio group, the blockiness value (Rc) of Resomer® RG 756S (Rc: 1.7) was highest in its group; whereas for the 50/50 acid end-capped group, Expansorb® DLG 50-2A (Rc: 1.9) displayed notably higher values than their counterparts. Expansorb® 50-2E (LL: 2.5, LG: 2.6)and Resomer®RG 502 (LL: 2.6, LG: 2.5) showed the lowest block lengths, suggesting they may undergo a steadier hydrolytic process compared to random, heterogeneously distributed PLGA.
Highlights
IntroductionPolymeric biomaterials are widely used in commercial biomedical products in the past several decades.[1, 2] Poly(lactic-co-glycolic acid) or poly(lactide-co-glycolide) (PLGA) is a thermoplastic co-polyester comprised of various ratios of its monomers and is hydrolyzed in vivo into non-toxic lactic and glycolic acid, that are metabolized in the tricarboxylic acid cycle and eliminated via carbon dioxide and water.[3,4,5] Due to its biocompatibility, biodegradability, and ease of processing, PLGA has been further developed in areas such as tissue engineering (e.g., bone regeneration,[6,7,8,9] wound dressing,[10,11,12] vascular grafting13, 14), medical imaging,[15, 16] and drug delivery,[17,18,19] especially for long-acting release formulations.[20,21,22] Several widely used PLGA-based commercial medical devices 23 and drug products have been developed, such as Supralimus®,24 a coronary sirolimus-eluting stent coated with a blend of PLGA/PLA/PVP, and the Lupron Depot® microspheres and Zoladex® implant,[25, 26] both of which are luteinizing hormone-releasing hormone analog, continuous long-acting release formulations.Nuclear magnetic resonance (NMR) spectroscopy, the physical phenomenon of nuclei in a magnetic field first observed by F
Three representative 1HNMR spectra of Poly(lactic-co-glycolic acid) (PLGA) polymers with different L/G ratios are shown in Figure 1, where A, B and C represent the spectrum of Expansorb® DLG 50-5A, Expansorb® DLG 752A and Expansorb® DL 100-2A, respectively
Four important properties describing the chemical microstructures of 17 commercial PLGA polymers across 5 different brands and varying L/G ratio, end-capping, and molecular weights have been investigated by 1H and 13CNMR spectroscopy
Summary
Polymeric biomaterials are widely used in commercial biomedical products in the past several decades.[1, 2] Poly(lactic-co-glycolic acid) or poly(lactide-co-glycolide) (PLGA) is a thermoplastic co-polyester comprised of various ratios of its monomers and is hydrolyzed in vivo into non-toxic lactic and glycolic acid, that are metabolized in the tricarboxylic acid cycle and eliminated via carbon dioxide and water.[3,4,5] Due to its biocompatibility, biodegradability, and ease of processing, PLGA has been further developed in areas such as tissue engineering (e.g., bone regeneration,[6,7,8,9] wound dressing,[10,11,12] vascular grafting13, 14), medical imaging,[15, 16] and drug delivery,[17,18,19] especially for long-acting release formulations.[20,21,22] Several widely used PLGA-based commercial medical devices 23 and drug products have been developed, such as Supralimus®,24 a coronary sirolimus-eluting stent coated with a blend of PLGA/PLA/PVP, and the Lupron Depot® microspheres and Zoladex® implant,[25, 26] both of which are luteinizing hormone-releasing hormone analog, continuous long-acting release formulations.Nuclear magnetic resonance (NMR) spectroscopy, the physical phenomenon of nuclei in a magnetic field first observed by F. Bloch and E.M. Purcell who received the Nobel Prize in physics in 1952,27, 28 has been explored in various areas such as pharmaceutical analysis and clinical diagnostics.[29] Similar to other forms of spectroscopy, NMR spectra results from the transitions between different energy states of the dipole-carrying atomic nuclei isotopes (1H, 13C, 15N and 31P).[30, 31] NMR technology is highly specific, precise, and non-invasive, and is well-established for structural elucidation and confirmation of small to large molecules.[32,33,34] Combined with quantitative analysis, NMR methods have been further used in pharmaceutics and pharmacokinetics to determine composition, impurities, and metabolites.[35, 36] Another sub-field in which NMR is heavily applied is polymer science. Several studies have used NMR spectroscopy to characterize copolymers such as PLGA to determine their solubility, amphiphilicity and hydrolysis mechanism/rate.[40,41,42] As an example, Garner et al.[43] have reported an analytical protocol to confirm the key properties of PLGAs used in commercial drug products, namely the ratio of lactic and glycolic acid (L/G ratio) and nature of polymer end-capping
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
