PCL-PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems.

The development of flexible drug delivery systems that can be tuned as a function of the drug to be delivered and of the target disease is crucial in modern medicine. For this aim, novel amphiphilic poly(ε-caprolactone)-g-poly(ethylene glycol) (PCL-g-PEG) copolymers with well-controlled design were synthesized by thiol-yne photochemistry. The grafting density and the copolymer amphiphilicity were easily controlled via the reaction parameters: concentration, reaction time, PEG length and the molar ratio between PCL and PEG or the photoinitiator in the reaction mixture. The self-assembling behavior of the copolymers was studied and a correlation between the composition of PCL-g-PEG and the nanoaggregate diameter sizes (28 to 73 nm) and critical aggregation concentrations (1.1 to 4.3 mg L-1) was found. The influence of copolymer amphiphilicity on the drug loading was evaluated with various drugs including anticancer drugs (paclitaxel, ABT-199), drugs to overcome multidrug resistance in cancer cells (curcumin, elacridar), an anti-inflammatory drug (dexamethasone) and an antibacterial drug (clofazimine). Finally, the influence of amphiphilicity on curcumin release and toxicity towards MCF-7 cancer cell lines was studied. The impact of the grafting density, PEG length and the overall EG/CL ratio is discussed in detail. Curcumin loaded PCL-g-PEG with lower EG/CL ratios and shorter PEG chains showed higher toxicity compared to their more hydrophilic counterparts.

Estimation of width of narrow molecular-weight distributions by size-exclusion chromatography with concentration and light scattering detection.

A new method for the estimation of the weight-to-number-average molecular-weight ratio, Mw/Mn of polymers with a narrow molecular-weight distribution, approximated by log-normal distribution, is proposed using size-exclusion chromatography (SEC) with concentration and light-scattering detectors. From experimental data, the Mw/Mn ratios are calculated by two procedures: one using the concentration and light-scattering elution curve for the polymer measured, and the other based on the concentration elution curve and calibration line for a wide range of molecular masses. An iteration method has been developed making the two Mw/Mn ratios converge. The method was applied to a series of narrow molecular-weight distribution polystyrene standards.

Influence of peak-broadening and interdetector volume error on size-exclusive chromatographic analysis with dual viscometric-concentration detection using the universal calibration method.

The effect of peak-broadening and error in interdetector volume on the local calibration curve and experimental molecular-mass averages obtained by size-exclusion chromatography (SEC) with dual concentration/viscosity detection, and determination of molecular mass using the universal calibration (UC) method, is theoretically examined using a polymer sample with a molecular-mass distribution (MMD) approximated by the log-normal function. Although peak-broadening is often neglected, its effect on the slope of the local calibration curve and, consequently, on the experimentally obtained values of the weight-to-number average ratio is large. To obtain the right values of these parameters, a numerical correction is usually recommended. While using the UC method, the relationships between the extent of peak broadening, calibration slopes and interdetector volume are complex and can contribute to the occurrence of undiscovered errors. For this reason, an understanding of this problem, using a model, is necessary. The results of the UC method are compared with those obtained using dual-detection with known Mark-Houwink-Kuhn-Sakurada parameters (MHKS method), light-scattering (LS)/concentration detection as well as with the results obtained using conventional calibration. Due to peak-broadening, the slope of a local calibration curve and the weight-to-number average ratio, (Mw/Mn)", obtained using the UC method, increase compared to the theoretical values, whereas they decrease using the MHKS or LS methods. The increase when using the UC method is even larger compared to evaluation using conventional calibration. The effect of the error in interdetector volume on the slopes of local calibrations and the weight-to-number average ratios is opposite in the UC method to that found using the MHKS and LS methods.

Phase transition parameters of potential thermosensitive drug release systems based on polymers of N-alkylmethacrylamides.

The phase separation and its thermohysteresis in dilute aqueous solutions of polymeric components of potential drug release systems (homopolymers and copolymers of N-isopropylacrylamide, N-isopropylmethacrylamide, N-propylmethacrylamide, N-sec-butylmethacrylamide, and N-(2-hydroxypropyl)methacrylamide) was studied, both on heating and cooling. Plots of light transmittance vs temperature were constructed and the parameters characterizing them were correlated with polymer structures. Qualitative information was obtained on the rate of formation of the concentrated phase on heating and its disappearance on cooling. Attention has been drawn to the improper identification of the cloud-point temperature, measured at an arbitrary concentration, with the lower critical solution temperature (LCST) as is frequently found in papers dealing with biomedical applications of thermosensitive polymers.