Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

Abstract

Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R=0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system.

Docetaxel loaded mPEG-PLA nanoparticles for sarcoma therapy: preparation, characterization, pharmacokinetics, and anti-tumor efficacy

“…The drug release rate slowed down with the increase of polymers' molecular weight. Theoretically, the degradation rate of the polymer decreased with the increase of its molecular weight that slowed the drug release rate (Bohr et al, 2017). So, the drug release profile in the study was in accordance with the theory.…”

In Vivo Degradation Mechanisms of Aliphatic Polycarbonates and Functionalized Aliphatic Polycarbonates

“…PEC is a rubbery and amorphous polymer with a glass transition temperature of 15-17°C. [31,32] PTMC is readily synthesized through the ring-opening polymerization of trimethylene carbonate in the presence of a variety of metal, [33][34][35][36] organo, [37,[38][39][40] and enzyme [41] catalysts, and can also be polymerized in the absence of a catalyst. [34,39,42] It is a rubbery and amorphous polymer, with a glass transition temperature of from −26 to −15°C, for number average molecular weights of 7 and 42 kDa, respectively.…”

“…Moreover, SEM images of the surface of extracted implants showed that the initially smooth surfaces were extensively pitted. [31,32,61,64] Finally, when macrophages were cultured on the surfaces of high (>100 kDa) molecular weight PEC [65,66] and PTMC, [67,68] the polymer surfaces were also pitted where the cells had adhered.…”

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

“…11,20,21 The enzyme solutions have also been shown to degrade PEC. 19,22 However, recently, the specific biodegradation mechanism of PEC has been confirmed, in which macrophages primarily secrete reactive oxygen species (ROS) rather than enzymes to erode PEC. 23 In contrast, the degradation mechanism of PTMC remains ambiguous.…”