Investigation of factors influencing the hydrolytic degradation of single PLGA microparticles

Abstract

9Poly lactide-co-glycolide (PLGA) is an important polymer matrix used to provide sustained 10 release across a range of active pharmaceutical ingredients (APIs) and works by hydrolytic 11 degradation within the body, thereby releasing entrapped drug. Processing and sterilisation 12 can impact on the morphology and chemistry of PLGA therefore influencing the hydrolysis 13 rate and in turn the release rate of any entrapped API. This paper has looked at the effect of 14 supercritical carbon dioxide (scCO 2 ) processing, gamma irradiation, comonomer ratio and 15 temperature on the hydrolysis of individual PLGA microparticles, using a combination of 16 Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) imaging, Scanning 17 Electron Microscopy (SEM), Differential Scanning Calorimetery (DSC) and Gel Permeation 18 chromatography (GPC) to facilitate a better understanding of the physiochemical factors 19affecting the hydrolysis rate. This work has shown that scCO 2 processing influences 20 hydrolysis rates by increasing the porosity of the PLGA microparticles, increasing the lactide 21 comonomer ratio decreases hydrolysis rates by reducing the hydrophilicity of the PLGA 22 microparticles and increasing the gamma irradiation dose systematically increases the rate of 23 hydrolysis due to reducing the overall molecular weight of the polymer matrix via a chain 24 scission mechanism. Moreover this work shows that ATR-FTIR imaging facilitates the 25 determination of a range of physicochemical parameters during the hydrolysis of a single 26 PLGA microparticle including water ingress, water/polymer interface dimensions, 27 degradation product distribution and hydrolysis rates for both lactide and glycolide 28 copolymer units from the same experiment. 29

The impact of monomer sequence and stereochemistry on the swelling and erosion of biodegradable poly(lactic-co-glycolic acid) matrices

“…PLGA performance has been examined in a variety of constructs including microparticles [39,45], films [46,47] and solid matrices in a variety of geometries [33,48]. For the current studies, which focus on bulk properties rather than drug release, we have chosen to fabricate the polymers into macroscale cylindrical matrices to increase their relevance to larger implantable devices, e.g., screws and plates.…”

Microparticles for controlled growth differentiation factor 6 delivery to direct adipose stem cell‐based nucleus pulposus regeneration

“…Homo and copolymers of lactide and glycolide have found particular application as delivery vehicles as they are FDA-approved for various clinical functions (Middleton & Tipton, 2000), degrade in vivo into natural products (lactic and glycolic acid) that are processed by normal metabolic pathways (Göpferich, 1996;Lu et al, 2000), and have tuneable physico-chemical properties (Vo et al, 2012). Controlled release from MPs formed from polymers such as poly(DL-lactic acid-co-glycolic acid) (PLGA) is typically dependent upon the degradation rate, which in turn can be altered by changing the lactide: glycolide ratio or molecular weight (Keles, Naylor, Clegg, & Sammon, 2015). Previously, we have developed improved methods for growth factor delivery by decoupling release kinetics from polymer degradation by the inclusion of a more hydrophilic component, such as polyethylene glycol (PEG; White et al, 2013).…”

Co-electrospraying of tumour cell mimicking hollow polymeric microspheres for diffusion magnetic resonance imaging

“…A previous study has reported that PLGA microparticles with higher hydrophilicity often show a faster degradation rate in an aqueous medium. [51] The hydrophilic property of PLGA can be modified by forming a copolymer with PEG, which has been widely used in controlled drug delivery carrier, for example PEG-PLGA micro/nanoparticles. [23,30] Therefore in this study, three types of PLGA polymers with different ratios of glycolic acid-to-lactic acid were chosen to investigate the formability of solid spherical particles in electrospraying (denoted as PLGA-1, PLGA-2 and PLGA-3 in the Materials section).…”