Characterization And Degradation Behaviors Of Nanoparticles Of Amphiphilic PEG-PCL Copolymers As Durg Carriers

Recently, amphiphilic block copolymers are of growing interest in the field of temporary therapeutic application as drug delivery carriers and environment protection. These carriers are attractive due to their size, stability, versatility, and biocompatibility. Nanoparticles, especially micelles, made of biodegradable and biocompatible amphiphilic block copolymers such as poly (lactic acid)-poly (ethylene glycol) (PLA-PEG), poly (ε-caprolactone)-poly (ethylene glycol) (PCL-PEG), and PCL-PLA-PEG, have been the subject of growing scientific attention in recent years. The physical architecture of polymer is important in drug carrier design. The stability and degradation of micelles in aqueous solutions affect their drug encapsulation efficiency and drug release characteristics.Amphiphilic, linear (diblock and triblock) and star shaped (3-arm and 4-arm) PEG-PCL were synthesized by ring-opening polymerization ofε-caprolactone with stannous octoate as a catalyst, in the presence of monomethoxypoly(ethylene glycol)(MPEG), PEG, 3-arm PEG and 4-arm PEG as an initiator, respectively. The monomer to initiator ratio was varied to obtain copolymers with various PEG weight fractions. The molecular weight and chemical structure were investigated by nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC) and the results confirmed that the product had expected structure. The self-aggregation behaviors of the copolymers were studied. The sizes and polydispersity of nanoparticles prepared by the precipitation/solvent evaporation technique in PBS solution were determined by Dynamic light scattering (DLS). The average hydrodynamic diameters were in the range of 15-35 nm and the size distribution was narrow and unimodal indicating that PEG-PCL form uniform nanoparticles. It was observed that the sizes of nanoparticles increased with PCL contents. The morphology of 3-arm PEG-PCL copolymeric nanoparticles was monitored by atomic force microscopy (AFM). We found the morphology of nanoparticles was close to sphericity. The nanoparticles showed a dark core around with bright corona in the phase image, in which the dark domains correspond to hard phase due to water insoluble PCL segments and the bright coronas due to the PEG coronas. 1H NMR spectrum of PEG-PCL copolymeric nanoparticles in D2O showed that the PCL blocks were in a highly condensed state. These results indicated that the copolymers in aqueous environment tended to self-assemble to form the nanoparticles with inner insoluble PCL blocks and outer soluble PEG blocks.The hydrolytic degradation of PEG-PCL copolymeric nanoparticles in phosphate buffered solution (PBS solution, pH 7.4) at 37℃was examined over a period of about six months. We investigated the hydrolytic degradation behaviors of linear and star-shaped PEG-PCL polymeric nanoparticles from different points of view by using DLS, 1H NMR and GPC. This result suggests that degradation mechanism of nanoparticles is quite faster than that of bulk materials. The degradation ratio increased faster for the copolymer with shorter PCL block length. In general, the PEG segments are highly hydrated, water can cross the PEG shell freely and contact the interface region of PCL core and PEG shell; on the other hand, water cannot penetrate the inner part of the PCL core due to the hydrophobic character. The initial hydrolysis degradation mainly occurs at the surface of PCL core. With degradation time extended, water can attack the PCL block easily due to some caves and channels in the PCL core formed by the cleavage of ester bonds, and more CL-CL, EO-CL ester bonds were cleaved. During degradation process, CL oligomers were produced and those with low molecular weight diffused into aqueous solution from the core of nanoparticles. Linear and star-shaped copolymers had different degradation speed due to their chemical structure.Copolymeric nanoparticles, which contained praziquantel (PZQ) as a model drug and MPEG-PCL as drug carriers, were prepared by the precipitation/solvent evaporation technique. The diameter of nanoparticles was measured by DLS and the diameter of drug-loaded nanoparticles was smaller than that of the corresponding drug-free nanoparticles. The drug loaded and drug-loading efficiency was affected by the length of hydrophobic block in copolymer.