Impact of changes in collagen construction and molecular state on integrin - binding properties.

The interaction between the integrin and collagen is important in cell adhesion and signaling. Collagen, as the main component of extracellular matrix, is a base material for tissue engineering constructs. In tissue engineering, the collagen structure and molecule state may be altered to varying degrees in the process of processing and utilizing, thereby affecting its biological properties. In this work, the impact of changes in collagen structure and molecular state on the binding properties of collagen to integrin α2ß1 and integrin specific cell adhesion were explored. The results showed that the molecular structure of collagen is destroyed under the influence of heating, freeze-grinding and irradiation, the triple helix integrity is reduced and molecular breaking degree is increased. The binding ability of collagen to integrin α2ß1 is increased with the increase of triple helix integrity and decays exponentially with the increase of molecular breaking degree. The collagen molecular state can also influences the binding ability of collagen to cellular receptor. The collagen fibrils binding to integrin α2ß1 and HT1080 cells is stronger than to collagen monomolecule. Meanwhile, the hybrid fibril exhibits a different cellular receptor binding performance from corresponding single species collagen fibril. These findings provide ideas for the design and development of new collagen-based biomaterials and tissue engineering research.

Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: in vitro and in vivo evaluations.

Sustained release of therapeutic agents into tumor cells is a potential approach to improve therapeutic efficacy, decrease side effects, and the drug administration frequency. Herein, we used the modified double-emulsion solvent evaporation (DSE) method to prepare a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS). The prepared rough PTX-PLGA-MS possessed microporous surface and highly porous internal structures, which significantly influenced the drug entrapment and release behaviors. The rough MS with an average particle size of 53.47 ± 2.87 µm achieved high drug loading (15.63%) and encapsulation efficiency (92.82%), and provided a favorable sustained drug release. The in vitro antitumor tests of flow cytometry and fluoroimmunoassay revealed that the rough PTX-PLGA-MS displayed effective anti-gliomas activity and enhanced the cellular PTX uptake through adsorptive endocytosis. Both in vitro and in vivo antitumor results demonstrated that the sustained-release PTX could induce the microtubules assembly and the over-expression of Bax and Cyclin B1 proteins, resulting in the microtubule dynamics disruption, G2/M phase arrest, and cell apoptosis accordingly. Furthermore, as the rough PTX-PLGA-MS could disperse and adhere throughout the tumor sites and cause extensive tumor cell apoptosis with one therapeutic course (12 days), they could reduce the system toxicity and drug administration frequency, thus achieving significant tumor inhibitory effects with rapid sustained drug release. In conclusion, our results verified that the rough PTX-PLGA-MS drug release system could serve as a promising treatment to malignant glioma.

Paclitaxel-loaded PLGA microspheres with a novel morphology to facilitate drug delivery and antitumor efficiency.

The aim of this study was to develop a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS) delivery system to enhance drug delivery and antitumor efficiency as well as reduce drug administration frequency. Therefore, different morphological types of PTX-PLGA-MS were prepared using a modified solvent evaporation technique. Morphology analysis confirmed the successful preparation of the smooth PTX-PLGA-MS with internal sporadic porosity, and the novel rough PTX-PLGA-MS with microporous surface and porous internal structures. The PTX drugs were distributed in the readily bioavailable state (amorphous) in PTX-loaded MS, which allowed fast drug release from MS following intratumoral administration. The drug entrapment and release behaviors indicated that the rough MS could provide enough hydrophobic space for PTX-loading and deep surface folds for fast matrices degradation, thus achieving a higher drug-loading efficiency (17.8%) and a rapid sustained drug release effect. Furthermore, the rough MS showed strengthened in vitro anti-hepatoma efficiency than that of free PTX and smooth MS. The in vivo studies indicated remarkable antitumor activity of rough MS (tumor inhibition rate = 58.33%) for at least 13 days after a single injection, which was because the rapid sustained-release drugs could induce the pro-apoptosis gene and protein expressions, cause extensive tumor cell apoptosis, and reduce the toxicity to normal tissues. In conclusion, the rough PTX-PLGA-MS drug delivery system with outstanding tumor growth inhibition effect could serve as a promising treatment for liver tumor.