The Degradation and Drug Release Mechanisms of Poly(ethylene glycol)-functionalised Poly(L-lactide) Polymers
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Poly(L-lactide) (PLLA) is a well-recognised bioresorbable polymer known to degrade after 1.5 to 5 years by hydrolysis. For certain medical device or drug delivery applications, it would be desirable to reduce this degradation time as strategies for tailoring degradation and drug release rates remain limited. This work aimed to examine a consistent series of polymers based on a large block of PLLA and small quantities of hydrophilic poly(ethylene glycol) (PEG) initiator. The polymers had PLLA number average molecular weight (Mn) values ranging between about 60 kDa and 200 kDa and PEG Mns ranging between 550 Da and 5000 Da giving very low PEG wt% values ranging between 0.1 and 1.5 wt%. There are currently no studies which consider high molecular weight PLLA polymers with small quantities of PEG for potential use in structural implants. Furthermore, reports in the literature do not consider the individual effects of PEG addition and PEG and PLLA lengths. The focus of this project was on the impact of processing, hydrolytic degradation and drug release on the morphological aspects of the materials. The materials were thoroughly characterised in their as-synthesised and processed forms. The assynthesised polymers were semi-crystalline and retained the unit cell of PLLA. The glass transition temperature (Tg) was significantly reduced by PEG functionalisation. After injection moulding, nuclear magnetic resonance (NMR) indicated that the PEG component was still present. The Mn of the PEG functionalised samples decreased by approximately two-fold compared with the as-synthesised materials while the PLLA control polymers, processed beyond 200 °C, were more affected as the processing temperature was increased. The degradation properties of the materials were considered. The processed materials were submerged in phosphate buffered saline (PBS) (pH = 7.4) at 37 °C over an 8-month degradation study. During hydrolytic degradation, PEG functionalisation resulted in an increased water uptake. Mass loss began in all polymers when the Mn fell below a threshold of about 20 kDa. In the PEG functionalised samples, the degree of crystallinity increased with time, facilitated by plasticisation from PEG and the increased water content. The molecular degradation rate, k for the PEG-functionalised polymers was dependent on the presence of PEG functionalisation but was little affected by PEG length or PLLA length in the ranges studied. The time taken to reach the critical Mn, and hence the time for mass loss to begin, therefore depended on both the initial Mn and the presence or absence of PEG functionalisation. In the presence of PEG, k, was dramatically enhanced: k for PEG-functionalised polymers fell in the range of 6 x