The use of amphiphilic copolymer in the solid dispersion formulation of nimodipine to inhibit drug crystallization in the release media: Combining nano-drug delivery system with solid preparations.

Solid dispersion is a widely used method to improve the dissolution and oral bioavailability of water-insoluble drugs. However, due to the strong hydrophobicity, the drug crystallization in the release media after drug dissolution and the resulted decreased drug absorption retards the use of solid dispersions. It is widely known that the amphiphilic copolymer can encapsulate the hydrophobic compounds and help form stable nano-dispersions in water. Inspired by this, we tried to formulate the solid dispersion of nimodipine by using amphipathic copolymer as one of the carriers. Concerning the solid dispersions, there are many important points involved in these formulations, such as the miscibility between the drug and the carriers, the storage stability of solid dispersions, the dissolution enhancement and so on. In this study, a systemic method is proposed. In details, the supersaturation test and the glass transition temperature (Tg) measurement to predict the crystallization inhibition, the ratios of different components and the storage stability, the interactions among the components were investigated in detail by nuclear magnetic resonance (1H NMR) and isothermal titration calorimetry (ITC) and, the final dissolution and oral bioavailability enhancement. It was found that the amphiphilic copolymer used in the solid dispersion encouraged the formation the drug loading micelles in the release media and, finally, the problem of drug crystallization in the dissolution process was successfully solved.

Self-Delivery Photodynamic Nanoinhibitors for Tumor Targeted Therapy and Metastasis Inhibition.

Simultaneous inhibitions of primary tumor growth and distant metastasis are very critical for cancer patients to improve their survival and cure rates. Although photodynamic therapy (PDT) shows great potential for primary tumor treatment, it often exacerbates hypoxia with a reduced therapeutic efficacy and subsequently contributes to carcinoma progression and metastatic dissemination. To solve these issues, self-delivery photodynamic nanoinhibitors (PNI) are developed for tumor targeted therapy and metastasis inhibition. PNI are composed of a carbonic anhydrase inhibitor (CAi), a hydrophilic poly(ethylene glycol) (PEG) linker, and a hydrophobic photosensitizer protoporphyrin IX (PpIX). Such self-delivery design of PNI avoids the premature release and heterogeneous distribution of CAi and PpIX to enhance the availability and synergism. Briefly, the CAi-based nanoinhibitors improve the selectivity of CAi for specific recognition and inhibition of tumor-associated isoform carbonic anhydrase (CA) IX, which would not only facilitate the targeted drug delivery of PNI but also regulate the hypoxia-induced signaling cascade and PDT resistance. Benefiting from the CA IX inhibition and targeted PDT, PNI exhibit a robust inhibitory effect on primary tumor growth and distant metastasis. This targeted self-delivery strategy sheds light on the photosensitizer-based molecular design to overcome the defect of traditional PDT.

Electrospun Poly (Aspartic Acid)-Modified Zein Nanofibers for Promoting Bone Regeneration.

BACKGROUND: Critical-sized bone defects raise great challenges. Zein is of interest for bone regeneration, but it has limited ability to stimulate cell proliferation. In this regard, a poly (aspartic acid) (PAsp)-zein hybrid is promising, as PAsp can promote rat bone marrow stromal cell (rBMSCs) proliferation and osteogenic differentiation. This research aimed to develop electrospun PAsp-modified zein nanofibers to realize critical-sized bone defects repair. METHODS: Three groups of PAsp-modified zein nanofibers were prepared, they were PAsp grafting percentages of 0% (zein), 5.32% (ZPAA-1), and 7.63% (ZPAA-2). Using rBMSCs as in vitro cell model and SD rats as in vivo animal model, fluorescence staining, SEM, CCK-8, ALP, ARS staining, µCT and histological analysis were performed to verify the biological and osteogenic activities for PAsp-modified zein nanofibers. RESULTS: As the Asp content increased from 0% to 7.63%, the water contact angle decreased from 129.8 ± 2.3° to 105.5 ± 2.5°. SEM, fluorescence staining and CCK-8 assay showed that ZPAA-2 nanofibers had a superior effect on rBMSCs spreading and proliferation than did zein and ZPAA-1 nanofibers, ALP activity and ARS staining showed that ZPAA-2 can improve rBMSCs osteogenic differentiation. In vivo osteogenic activities was evaluated by µCT analysis, HE, Masson and immunohistochemical staining, indicating accelerated bone formation in ZPAA-2 SD rats after 4 and 8 weeks treatment, with a rank order of ZPAA-2 > ZPAA-1 > zein group. Moreover, the semiquantitative results of the Masson staining revealed that the maturity of the new bone was higher in the ZPAA-2 group than in the other groups. CONCLUSION: Electrospun PAsp-modified zein can provide a suitable microenvironment for osteogenic differentiation of rBMSCs, as well as for bone regeneration; the optimal membrane appears to have a PAsp grafting percentage of 7.63%.