Xing Zhou

Cyclodextrin-derived pH-responsive nanoparticles for delivery of paclitaxel.

Engineering of pH-responsive nanoplatforms can be facilely achieved from acetalated α-cyclodextrin materials. The hydrolysis period of nanoparticles can be precisely tailored by using materials with various acetal types that can be easily controlled by acetalation time. These nanomaterials with pH-modulated hydrolysis and pH-triggered drug delivery capability show good biocompatibility in vitro and in vivo. Incorporation of anticancer drug paclitaxel (PTX) into newly developed pH-sensitive nanosystems leads to nanotherapeutics with significantly improved cytotoxic activity against various tumor cells. Importantly, thus formulated nanomedicines can reverse the multidrug resistance of PTX-resistant cancer cells. In vivo antitumor studies also reveal the superior of pH-sensitive nanosystems over pristine PTX and pH-insensitive PLGA nanoformulations. Moreover, comparison with other two acid-labile materials evidenced the advantages of cyclodextrin-based nanovehicles with respect to drug loading capacity, in vitro and in vivo activity as well as alleviated adverse effects. These pH-responsive nanoparticles may serve as new generation nanocarriers for drug delivery.

A facile route to diverse assemblies by host–guest recognition

Self-assembly provides a powerful approach for generating complex materials with advanced functionalities. Currently it remains a great challenge to create hierarchically structured assemblies from materials with simple molecular structure. Further, successful clinical translation of polymer assemblies-based therapeutics requires facile yet effective strategies for their fabrication and cargo loading based on structurally simple and cost-effective starting materials. Herein we partly addressed these issues by an all-in-one strategy involving host–guest assembly via molecular recognition, in which carboxyl-bearing compounds serve as guest molecules, while N-substituted acrylamide homopolymers or their various copolymers are host materials. Assembly and therapeutic loading can be simultaneously realized by this one-pot approach, leading to superstructures across length scales and with multiple morphologies, such as micelle-like nanoparticles, vesicles, nano- and microspheres, microtubes, and onion-like multilayer structures. In addition to biomedical applications, superstructures generated by this simple and robust strategy have potential uses in templated synthesis, catalysis, optics, and microelectronics.

Assembled nanomedicines as efficient and safe therapeutics for articular inflammation.

Highly efficient nanomedicines were successfully fabricated by the indomethacin (IND) directed self-assembly of β-cyclodextrin (β-CD)-conjugated polyethyleneimine (PEI-CD), taking advantage of the multiple interactions between drug and polymer. These nanoscaled assemblies exhibited spherical shape and positively charged surface. Compared with the commercial tablet, the relative oral bioavailability of IND-nanomedicines was significantly enhanced. Evaluation based on either carrageenan-induced paw edema or complete Freunds adjuvant (CFA)-induced arthritis suggested the newly developed nanomedicines were more effective than raw IND or IND tablet in terms of prophylactic effect and therapeutic activity. Even the low dose of nanomedicines offered the comparable results to those of control groups at the high dosage in most cases. Moreover, the nanoformulation exhibited ameliorated gastrointestinal stimulation. All these positive results indicated that this type of nanomedicines might serve as a highly efficient and effective delivery nanoplatform for the oral delivery of water-insoluble therapeutics.

Facile engineering of nano- and microparticles viaself-assembly of homopolymers

We report an unprecedented assembling performance of amide-containing, homo-structured poly(N-alkylacrylamide)s, through which they can assemble into discrete spherical particles with size ranging from tens of nanometres to several micrometres. For a specific polymer, a facile control over topology and scale of assembled structures can be accomplished viasolvent conditions. Assembling using appropriate solvent gives rise to capsule-like assemblies. The molecular structure of polymers, such as the side chain chemistry and topology display striking impact on the size and morphology of resulting assemblies. These polymers might function as novel model systems for investigating complex functions performed by amide moieties in proteins, while this assembling offers a simple, facile but powerful and cost-effective manufacturing route for nano- or microstructured materials that may find great potential in diverse applications varying from cosmetics, drug delivery, nanomedicine, to biotechnology.

Facile route to versatile nanoplatforms for drug delivery by one-pot self-assembly.

There is still unmet demand for developing powerful approaches to produce polymeric nanoplatforms with versatile functions and broad applications, which are essential for the successful bench-to-bedside translation of polymeric nanotherapeutics developed in the laboratory. We have discovered a facile, convenient, cost-effective and easily scalable one-pot strategy to assemble various lipophilic therapeutics bearing carboxyl groups into nanomedicines, through which highly effective cargo loading and nanoparticle formation can be achieved simultaneously. Besides dramatically improving water solubility, the assembled nanopharmaceuticals showed significantly higher bioavailability and much better therapeutic activity. These one-pot assemblies may also serve as nanocontainers to effectively accommodate other highly hydrophobic drugs such as paclitaxel (PTX). PTX nanomedicines thus formulated display strikingly enhanced in vitro antitumor activity and can reverse the multidrug resistance of tumor cells to PTX therapy. The special surface chemistry offers these assembled entities the additional capability of efficiently packaging and efficaciously transfecting plasmid DNA, with a transfection efficiency markedly higher than that of commonly used positive controls. Consequently, this one-pot assembly approach provides a facile route to multifunctional nanoplatforms for simultaneous delivery of multiple therapeutics with improved therapeutic significance.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Nanoassemblies from homostructured polypeptides as efficient nanoplatforms for oral drug delivery

UNLABELLED The assembly of homostructured polypeptides bearing various side groups into well-defined nanostructures was presented, with their size and topology mainly dominated by the chemical structure and molecular weight of peptides. Pharmacokinetic and pharmacodynamic studies based on rat models suggested these newly constructed nanoassemblies with low cytotoxicity may function as novel nanoplatforms to efficiently and safely deliver therapeutics to achieve better efficacy but lower side effects. Other applications in biomedical fields, such as biotechnology, medical imaging, and tissue engineering, may also be expected. FROM THE CLINICAL EDITOR This research team investigated the assembly of homostructured polypeptides bearing various side groups into well-defined nanostructures, and demonstrated low cytotoxicity in rat disease models, suggesting that these novel nanoplatforms may safely and efficiently deliver therapeutics with low side effects.

Multiple noncovalent interactions mediated one-pot therapeutic assemblies for the effective treatment of atherosclerosis

Atherosclerosis may cause life-threatening coronary artery disease, carotid artery disease, stroke, and peripheral vascular disease, while its effective therapy remains challenging thus far. With the aim of facilely constructing efficacious and translational oral delivery systems for an anti-atherosclerotic drug of rapamycin (RAP), an all-in-one approach was created. This strategy involves a carboxyl-bearing compound (serves as a guest molecule) mediated self-assembly of a structurally simple host polymer of poly(N-isopropylacrylamide) (PNIPAm). The formation of microspheres and highly efficient packaging of RAP could be simultaneously achieved by this host-guest self-assembly, affording cost-effective therapeutic assemblies with particularly robust drug loading capacity, desirable drug dissolution, relative manufacturing simplicity, good lyophilization-reconstitution character, and facile scalability. Besides these pharmaceutical characteristics superior over control microspheres based on poly(lactide-co-glycolide) or a enteric coating material, therapeutic RAP microspheres fabricated by this assembly approach had high oral bioavailability. More importantly, assembled RAP microspheres displayed significant therapeutic advantages upon treatment of atherosclerosis in an apolipoprotein E-deficient mouse model. In addition, a long-term treatment with either RAP-containing assemblies or the carrier material PNIPAm revealed a good safety profile in mice post oral delivery. Accordingly, RAP microspheres developed herein are promising and translational therapeutics for atherosclerotic diseases. This study also provides new insights into the design of effective carrier materials for various lipophilic therapeutics.