The development of novel thermo-, pH- and reduction-sensitive polymeric micelles based on a block copolymer p(PEG-MEMA-co-Boc-Cyst-MMAm-co-VI)-b-PEG (PPBV) for the intracellular delivery of anticancer drugs is reported. The pH/temperature-responsive behaviour of PPBV is observed by both DLS and UV-Vis experiments. The PPBV micelles prepared by a quick heating process are stable in PBS (pH 7.4, 37 °C) for over 48 h and are stable in the presence of serum for at least 12 h. Paclitaxel (PTX) was loaded into the PPBV micelles with a high encapsulation efficiency (>85%), resulting in a high drug loading content (up to 26 wt%) by a simple heating method. The PTX-loaded micelles show slow drug release in PBS and rapid release after exposure to a weakly acidic pH or reductive environment. The PTX-loaded micelles showed higher cytotoxicity against HepG2 cells with increasing PTX concentration, whereas empty micelles are found to be non-toxic. These multi-sensitive polymeric micelles may serve as promising carriers for cytostatic drugs.

Cinnamaldehyde, a natural product that can be extracted from a variety of plants of the genus Cinnamomum, exhibits excellent biological activities including antibacterial, antifungal, anti-inflammatory, and anticancer properties. To overcome the disadvantages (e.g., poor water solubility and sensitivity to light) or enhance the advantages (e.g., high reactivity and promoting cellular reactive oxygen species production) of cinnamaldehyde, cinnamaldehyde can be loaded into or conjugated with polymers for sustained or controlled release, thereby prolonging the effective action time of its biological activities. Moreover, when cinnamaldehyde is conjugated with a polymer, it can also introduce environmental responsiveness to the polymer through the form of stimuli-sensitive linkages between its aldehyde group and various functional groups of polymers. The environmental responsiveness provides the great potential of cinnamaldehyde-conjugated polymers for applications in the biomedical field. In this review, the strategies for preparing cinnamaldehyde-contained polymers are summarized and their biomedical applications are also reviewed.

The temperature responsive PEGylated polyaspartamide derivative, denoted as mPEG-PAAHP, was synthesized by the click reaction. FTIR and ¹H NMR were adopted to characterize and confirm the chemical structures of the obtained mPEG-PAAHPs. The temperature responsive behavior investigated by transmittance and dynamic light scattering showed that some of the obtained mPEG-PAAHPs exhibited obvious temperature responsiveness and could be used to prepare nanoparticles by quickly heating. Drug paclitaxel can be encapsulated into mPEG-PAAHP based nanoparticles with a high encapsulation efficiency up to 99% (corresponding to a drug loading content of around 9.9%). Dynamic light scattering results showed that the PTX-loaded nanoparticles had a mean size around 80 nm (PDI<0.2) and good stability in PBS with 150 mM ionic strength. In vitro cytotoxicity results showed that mPEG-PAAHP did not show any toxicity to HeLa cells, but the PTX-loaded nanoparticles based on mPEG-PAAHP exhibited obvious anti-cancer activity. Thus, the temperature responsive PEGylated polyaspartamide derivative mPEG-PAAHP may be a promising drug delivery system.