The anti-bacterial poly(caprolactone)-poly(quaternary ammonium salt) as drug delivery carriers.

Anti-bacterial materials play significant role in biomedical field. Researches and applications of new anti-bacterial materials are necessary. Novel linear and star-shaped copolymers of poly(caprolactone)-poly(quaternary ammonium salt) (PCL-PJDMA) were synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. The structures of the copolymers were confirmed by nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy. The copolymers self-assembled into ball-shaped micelles with low critical micelle concentration (10(-4) ∼ 10(-3) mg/ml). An anti-bacterial drug, triclosan, was chosen as a model drug to investigate the potential application of the copolymers in drug-controlled release. The anti-bacterial experiments against Escherichia coli indicated that all the copolymer micelles had anti-bacterial ability and drug-loaded star-shaped PCL-PJDMA micelles were the best. The slow release of the drug from the drug-loaded micelles prolonged anti-bacterial effect. Therefore, PCL-PJDMA themselves have not only anti-bacterial ability but also the copolymer micelles can be used as carriers for anti-bacterial drugs.

pH responsive micelles based on copolymers mPEG-PCL-PDEA: The relationship between composition and properties.

Polymeric micelles with pH response are considered as promising drug carriers for cancer therapy. In this study, copolymers methoxy-poly (ethylene glycol)-b-poly (ε-caprolactone)-b-poly (diethylaminoethyl methacrylate) (mPEG-PCL-PDEA) were designed and synthesized to investigate the relationship between number of pH responsive units and micelle properties. The structures of these copolymers were characterized by nuclear magnetic resonance, Fourier transform infrared, gel permeation chromatograph, differential scanning calorimetry and water contact angle. The micelles of the copolymers were obtained, the micelle properties were studied by critical micellization concentration, micelle size, morphology, pH response, cytotoxicity and drug loading/release. Moreover, dissipative particle dynamics (DPD) was used to investigate the structure of the micelles under different pH. The results showed that the micelle properties including pH sensitivity, cytotoxicity and drug loading/releasing performance, were related to PDEA units in copolymers. So, mPEG-PCL-PDEA micelles with suitable composition are promising as drug carriers due to their high pH sensitivity, low cytotoxicity and good drug loading/releasing performance.

Effect of amphiphilic PCL-PEG nano-micelles on HepG2 cell migration.

Uptake of nanoparticles (NPs) affects cell migration but the mechanism remains poorly understood. In this study, the amphiphilic block PCL-PEG nano-micelles with well-controlled hydrophilic/hydrophobic chains were used to investigate the effect of internalized nano-micelles on cancer cell migration. Our results indicated that the nano-micelles with medium PCL and PEG chains increased expression of Rho GTPases and impeded focal adhesion components. This could enhance Hep G2 cell motility. The nano-micelles with large PCL and PEG chains showed lower Rho GTPase levels and higher FA components. This is consistent with slower cell migration. Understanding the mechanism of NPs regulating cell behaviors may help the design of efficient drug delivery systems based on polymer micelles.

Synthesis of amphiphilic copolymers containing zwitterionic sulfobetaine as pH and redox responsive drug carriers.

Amphiphilic poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate)-r-poly(N-(3-sulfopropyl)-N-methacrylate-N,N-diethylammonium-betaine) (PCL-SS-PDEASB) was designed and synthesized successfully. pH and redox dually responsive micelles were prepared based on the obtained copolymers, with zwitterionic sulfobetaines as hydrophilic shell, DEA as pH sensitive content and disulfide as redox responsive linkage. The micelle diameters were all less than 200 nm and the micelle diameter distributions were narrow. These micelles could be triggered by pH and redox condition. The drug release from the drug-loaded micelles displayed fastest under simultaneously acidic and reductive conditions. Results of in vitro cell toxicity evaluation showed that introduction of sulfobetaines could greatly decrease the toxicity of poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate) (PCL-SS-PDEA) micelles. DOX-loaded PCL-SS-PDEASB micelles showed higher efficiency to kill HeLa cells than DOX-loaded PCL-PDEASB micelles. Half inhibitory concentration (IC50) of DOX-loaded PCL-SS-PDEASB micelles decreased with the content of sulfobetaines increasing and was even closer to that of DOX·HCl. Thus, the pH and redox dually responsive biodegradable micelles generated by PCL-SS-PDEASB may be potential smart drug carriers for tumor targeted delivery.