Xinyu Peng

Functionalization of biodegradable hyperbranched poly(α,β-malic acid) as a nanocarrier platform for anticancer drug delivery

Multiple functionalization of nanoparticles has attracted great interest in drug delivery. In this paper, biodegradable poly(α,β-malic acid) with a hyperbranched architecture was synthesized via the polycondensation of L-malic acid, the functionalized poly(α,β-malic acid) was used as a nanocarrier platform with the immobilization of poly(ethylene glycol) (PEG) for long circulation, cinnamyl alcohol (CIN) for introducing π–π stacking interactions and 1-(3-aminopropyl)imidazole (API) for pH-sensitivity. The conjugates self-assembled into nanoparticles to load anticancer drug doxorubicin (DOX). The morphology, mean size and size distribution, drug release profile and in vitro anticancer activity of DOX loaded nanoparticles were studied. The results showed that the mean size of the nanoparticles was below 200 nm, the drug loading content was higher than 10 wt% and it increased with increasing CIN content because of the π–π stacking interaction between DOX and the carriers. The drug release of the nanoparticles was faster in the medium with pH 6.0 compared to pH 7.4. The nanoparticles exhibited an endosomal escape function to accelerate the release of DOX in cancer cells, which resulted in low IC50s to kill 4T1 breast cancer cells and HepG2 liver cancer cells in vitro.

Chain length effect on drug delivery of chrysin modified mPEG–PCL micelles

Four chrysin modified mPEG–PCL block copolymers with different chain lengths of mPEG and PCL blocks were synthesized and self-assembled into micelles to load the anticancer drug doxorubicin (DOX). The effect of block chain length on drug delivery was investigated. The four block copolymers were characterized by 1H NMR, GPC and DSC. The drug loading contents of all the micelles were higher than 20%, the mPEG2k–PCL5k–CHS micelles showed the highest drug loading content and encapsulation efficiency of 26.8% and 93%, respectively. The micelles were spherical with the size increasing after drug encapsulation, and the mean size of the drug loaded micelles was around 100 nanometers. π–π stacking interactions between the micelles and DOX was invoked. The mPEG2k–PCL5k–CHS micelles exhibited the best profile for sustained-release. The cellular uptake and IC50 revealed that the DOX loaded mPEG2k–PCL5k–CHS micelles showed the best anticancer activity in vitro.

Biodegradable poly(ethylene glycol)–poly(ε-carprolactone) polymeric micelles with different tailored topological amphiphilies for doxorubicin (DOX) drug delivery

Three poly(ethylene glycol)–poly(e-carprolactone) (PEG–PCL) copolymers with different topologies but identical molar ratio between PEG to PCL were designed. These copolymers, namely, diblock (L-PEG–PCL), triblock (B-PEG–PCL), and star shaped (S-PEG–PCL) copolymers, were extensively characterized by 1H Nuclear Magnetic Resonance (1H NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Gel Permeation Chromatography (GPC) analyses. The effect of topology on crystallization was investigated by X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC). Results showed that the diblock copolymer possessed the highest crystallinity, followed by triblock and star shaped copolymers. Although the topology did not affect the self-assembly behavior of copolymers, the effects on size, size distribution, drug loading content, and drug release rate of the polymeric micelles were observed. The micelles self-assembled from linear diblock copolymer achieved higher cellular uptake and lower half maximal inhibitory concentration (IC50). These findings are favorable to establish the foundation to further design proper structure of amphiphilic copolymers as nanocarrier systems for efficient anticancer therapy.

Synthesis, characterization, and crystallization of biodegradable poly(ε-caprolactone)-poly(L-lactide) diblock copolymers

Abstract Three diblock copolymers of PCL6k-PLLA2k, PCL6k-PLLA4k, and PCL6k-PLLA6k were prepared and their crystallization behaviors were investigated. The molecular weights of the copolymers calculated from 1H nuclear magnetic resonance spectra were equivalent to the designed molecular weights. The gel permeation chromatography spectra of the copolymers showed one peak, which revealed that the copolymers were monodisperse. The crystallization capability of poly(ε-caprolactone) (PCL) decreased and that of poly(L-lactide) (PLLA) increased when the molecular weight of the PLLA block was increased from 2k to 6k. PCL spherulites in the PCL6k-PLLA2k copolymer film were smaller than those in PCL6k-PLLA4k or PCL6k-PLLA6k copolymer film. PCL spherulites in the PCL6k-PLLA2k copolymer film grew fastest within all three diblock copolymers. An obvious phase separation phenomenon was observed on the surface of PCL6k-PLLA6k copolymer film in atomic force microscopy images.

Synthesis and Cytocompatibility of Biodegradable Poly (L-Lactide-r-5-Hydroxyl Trimethylene Carbonate) Copolymer

The biomedical applications of poly(L-lactide) (PLLA) were limited by its high crystallinity, hydrophobicity and lack of functional groups, which resulted in poor cell affinity. In this paper, L-lactide (85 mol%) and 5-benzyloxy-trimethylene carbonate (BTMC) (15 mol%) were copolymerized via ring-opening polymerization in the presence of stannous octanoate as catalyst. The copolymer was unprotected to receive poly(L-lactide-r-5-hydroxyl trimethylene carbonate) copolymer with functional hydroxyl pendant groups. The copolymer was characterized by 1H NMR, FTIR, GPC, DSC, TGA and XRD. The results showed that the reactivity of BTMC monomer was lower than that of LLA in the copolymerization. Both the protected and unprotected copolymers were amorphous. C2C12 myoblasts were seeded on the copolymer films to evaluate the cytocompatibility of the copolymer. The adhesion, proliferation and spreading of cells on poly(L-lactide-r-5-hydroxyl trimethylene carbonate) films were much better than those on PLLA films. The cell affinity of PLLA was improved greatly after the functionalization.

Synthesis, characterization, and property of biodegradable PEG-PCL-PLA terpolymers with miktoarm star and triblock architectures as drug carriers

A series of amphiphilic terpolymers with miktoarm star and triblock architectures of poly(ethylene glycol) (PEG), poly(ε-caprolactone) (PCL) and poly(l-lactide acid) (PLLA) or poly(DL-lactide acid) (PDLLA) terpolymers were synthesized as carriers for drug delivery. The architecture, molecular weight and crystallization behavior of the terpolymers were characterized. Anticancer drug doxorubicin was encapsulated in the micelles to investigate their drug loading properties. The miktoarm star terpolymers exhibited stronger crystallization capability, smaller size and better stability than that of triblock polymeric micelle, owing to the lower CMC values of miktoarm star polymeric micelle. Furthermore, the drug-loaded miktoarm star polymeric micelles showed the cumulative DOX release account of the micelles with PDLLA blocks was 65.3% while the release account of the corresponding micelles containing PLLA blocks was 45.2%. The IC50 values of drug-loaded miktoarm star polymeric micelle were lower than triblock polymeric micelle. Meanwhile, Confocal laser scanning microscopy (CLSM) and Flow Cytometry results demonstrated that the miktoarm star micelles were more favorable for cellular internalization. The miktoarm star micelles with PDLLA blocks were promising carriers for anticancer drug delivery.

Effective combination therapy of percutaneous ethanol injection and chemotherapy based on injectable low molecular weight gels

Abstract Percutaneous ethanol injection (PEI) therapy was used in liver cancer treatment, however, the therapeutic ethanol in PEI easily flew away from injected solid tumours and hinder the treatment effect. In this paper, injectable supramolecular gels formed by self-assembly of low molecular weight gelators (LMWGs) based on glycylglycine modified phenylboronic acid were prepared to localize ethanol and load chemotherapeutic drug for in situ synergistic therapy. The mechanism, morphology and rheological property of supramolecular gels were characterized by NMR, UV, SEM, etc. The rheological study revealed that the gels were formed in situ rapidly and recovered promptly once damaged. The gels were non-toxicity to both normal 3T3 fibroblasts cells and 4T1 breast cancer cells. Doxorubicin (DOX) hydrochloride and ethanol were encapsulated in the gels for the combination of chemotherapy and PEI therapy. The in vivo anticancer activity of the DOX-loaded gels was carried out in tumour bearing mice. The injected gels were coated around tumour tissues to lock ethanol, and DOX was released sustainingly from the gels to maintain effective concentration to induce the apoptosis of tumour cells. DOX-loaded gels and the ethanol exhibited excellent therapeutic efficacy and low side effects in local cancer therapy.