Thermosensitive PNVCL‐b‐PEG block copolymer coupled with folic acid was prepared as an anti‐cancer drug carrier. This polymer self‐assembled into stable micelles in aqueous solutions at above 33 °C. At 37 °C, the release profile of PNVCL‐b‐PEG‐FA micelles showed a slower and more controlled release of the entrapped 5‐FU than that at 25 °C. The blank and 5‐FU‐loaded PNVCL‐b‐PEG‐FA micelles did not induce remarkable cytotoxicity against the EA.hy 926 human endothelial cell line; however, 5‐FU‐loaded PNVCL‐b‐PEG‐FA micelles showed a cytotoxicity effect against 4T1 mouse mammary carcinoma cells due to the availability of loaded anti‐cancer drugs delivered to the inside of the cancer cells by the folate‐receptor‐mediated endocytosis process.
An amphiphilic biodegradable polymer, poly(aspartic acid‐co‐lactic acid) (PAL), was synthesized by simply heating a mixture of aspartic acid (Asp) and L ‐lactide without additional catalysts or solvents. The unique branched architecture comprising succinimide units and lactic acid units was confirmed by IR and NMR spectroscopy. A copolymer of sodium aspartate and lactic acid (PALNa) was prepared by reacting PAL with an aqueous sodium hydroxide solution. The PAL was soluble in many organic solvents, while the PALNa was soluble in methanol and water. The hydrolytic degradation behavior of PAL varied with the copolymer composition. A higher Asp content resulted in a faster molecular weight decrease, and introducing glycolic acid units accelerated the degradation rate.
A biodegradable amphiphilic block copolymer, PEG‐b‐P(LA‐co‐MAC), was used to prepare spherical micelles consisting of a hydrophobic P(LA‐co‐MAC) core and a hydrophilic PEG shell. To improve their stability, the micelles were crosslinked by radical polymerization of the double bonds in the hydrophobic blocks. The crosslinked micelles had similar sizes and a narrow size distribution compared to their uncrosslinked precursor. The improved stability of the crosslinked micelles was confirmed by measurements of the CMC and a thermodynamic investigation. These micelles can internalize into Hela cells in vitro as demonstrated by inverted fluorescence microscopy and CLSM. These stabilized nanoscale micelles have potential use in biomedical applications such as drug delivery and disease diagnosis.
Mucoadhesive NP drug carriers have attracted substantial interest as a potential treatment for anterior eye diseases. NPs composed of PLA‐Dex surface functionalized with a mucoadhesive ligand, PBA, were developed as drug carriers with particle sizes ranging from 25 to 28 nm. Using CycA as a model drug, we showed that NPs encapsulated up to 13.7 wt% CycA and exhibited sustained release for up to 5 d in vitro at a clinically relevant dose. We fine‐tuned the PBA density on the NP surface to maximize the mucin‐NP interaction without compromising the particle stability in vitro. This block copolymer conjugate may be useful to improve the bioavailability of topical formulations.
Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer‐based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer—not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non‐biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated. 相似文献
A pH‐sensitive polymer was synthesized by introducing the N‐Boc‐histidine to the ends of a PLGA‐PEG‐PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N‐Boc‐histidine‐capped PLGA‐PEG‐PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un‐capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA‐MB‐435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N‐Boc‐histidine capped PLGA‐PEG‐PLGA might be a promising material for tumor targeting.
This paper aims to report the fabrication of biodegradable thin films with micro‐domains of cylindrical nanochannels through the solvent‐induced microphase separation of poly(L ‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(L ‐lactide) (PLA‐b‐PEG‐b‐PLA) triblock copolymers with different block ratios. In our experimental scope, an increase in each of the block lengths of the PLA and PEG blocks led to both a variation in the average number density (146 to 32 per 100 µm2) and the size of the micro‐domains (140 to 427 nm). Analyses by atomic force microscopy (AFM) and fluorescence microscopy indicated that the hydrophilic PEG nanochannels were dispersed in the PLA matrix of the PLA‐b‐PEG‐b‐PLA films. We demonstrated that the micro‐domain morphology could be controlled not only by the block length of PEG, but also by the solvent evaporation conditions.
A series of amphiphilic poly(L ‐leucine)‐block‐poly(ethylene glycol)‐block‐poly(L ‐leucine) (PLL‐PEG‐PLL) hybrid triblock copolymers have been synthesized. All the blocks in this system have good biocompatibility and low toxicity. The PLL‐PEG‐PLL copolymers could self‐assemble into micelles with PLL blocks as the hydrophobic core and PEG blocks as the hydrophilic shell, which were characterized by FT‐IR, 1H NMR, and transmission electron microscopy analysis. The critical micellar concentration of the copolymer was 95.0 mg · L−1. The circular dichroism spectrum shows that the PLL segments adopt a unique α‐helical conformation, which is found to play an important role in controlling the drug release rate. The drug release could be effectively sustained by encapsulation in the micelles. The copolymers may have potential applications in drug delivery.
