Construction of Eukaryotic Cell Biomimetics: Hierarchical Polymersomes-in-Proteinosome Multicompartment with Enzymatic Reactions Modulated Protein Transportation.

The eukaryotic cell is a smart compartment containing an outer permeable membrane, a cytoskeleton, and functional organelles, presenting part structures for life. The integration of membrane-containing artificial organelles (=polymersomes) into a large microcompartment is a key step towards the establishment of exquisite cellular biomimetics with different membrane properties. Herein, an efficient way to construct a hierarchical multicompartment composed of a hydrogel-filled proteinosome hybrid structure with an outer homogeneous membrane, a smart cytoskeleton-like scaffold, and polymersomes is designed. Specially, this hybrid structure creates a micro-environment for pH-responsive polymersomes to execute a desired substance transport upon response to biological stimuli. Within the dynamic pH-stable skeleton of the protein hydrogels, polymersomes with loaded PEGylated insulin biomacromolecules demonstrate a pH-responsive reversible swelling-deswelling and a desirable, on-demand cargo release which is induced by the enzymatic oxidation of glucose to gluconic acid. This stimulus responsive behavior is realized by tunable on/off states through protonation of the polymersomes membrane under the enzymatic reaction of glucose oxidase, integrated in the skeleton of protein hydrogels. The integration of polymersomes-based hybrid structure into the proteinosome compartment and the stimuli-response on enzyme reactions fulfills the requirements of eukaryotic cell biomimetics in complex architectures and allows mimicking cellular transportation processes.

Artificial Organelles with Orthogonal-Responsive Membranes for Protocell Systems: Probing the Intrinsic and Sequential Docking and Diffusion of Cargo into Two Coexisting Avidin-Polymersomes.

The challenge of effective integration and use of artificial organelles with orthogonal-responsive membranes and their communication in eukaryotic protocells is to understand the intrinsic membrane characteristics. Here, a novel photo-crosslinked and pH-responsive polymersome (Psome B) with 2-(N,N'-diisopropylamino)ethyl units in the membrane and its respective Avidin-Psome B hybrids, are reported as good candidates for artificial organelles. Biotinylated (macro)molecules are able to dock and diffuse into Avidin-Psome B to carry out biological activity in a pH- and size-dependent manner. Combined with another polymersome (Psome A) with 2-(N,N'-diethylamino)ethyl units in the membrane, two different pH-responsive polymersomes for mimicking different organelles in one protocell system are reported. The different intrinsic docking and diffusion processes of cargo (macro)molecules through the membranes of coexisting Psome A and B are pH-dependent as confirmed using pH titration-dynamic light scattering (DLS). Psome A and B show separated "open", "closing/opening", and "closed" states at various pH ranges with different membrane permeability. The results pave the way for the construction of multicompartmentalized protocells with controlled communications between different artificial organelles.

A Raman imaging-based technique to assess HPMC substituent contents and their effects on the drug release of commercial extended-release tablets.

In this study, we tried to assess the substitute contents of HPMC used in commercial extended-release tablets directly by an innovative Raman imaging-based analysis technique and find their effects on the in vitro performance of these pharmaceuticals. Twenty-seven batches of metformin hydrochloride extended-release tablets from various sources were collected in the Chinese mainland market. While Raman imaging was used to qualitatively analyze the composition of the tablets, the MeO and HPO contents of HPMC were quantitatively assessed by a newly proposed calculation method based on the Raman intensity of corresponding characteristic band. Additionally, the dissolution test was performed to evaluate the relationship between HPMC substitution pattern and in vitro behavior. In sum, our findings indicate that the drug release rate can be downregulated by increasing the MeO content of HPMC, while the high HPO content would largely eliminate the variation of drug release profiles among batches.