The effect of the extracellular vesicle loaded polylactic acid microspheres in promoting hepatocyte proliferation / 中国热带医学

@#Abstract: Objective　To prepare a microparticle delivery system that regulates the release rate of extracellular vesicles (EVs), and to exert long-term enhancement of liver cell proliferation after only one intervention. Methods EVs was extracted by differential centrifugation. The structure of the EVs was observed by transmission electron microscopy and the membrane marker protein of EVs was detected by Western blotting. EVs-PLA microspheres with "core-shell" structure were prepared by emulsion-solvent evaporation method. Scanning and transmission electron microscopy were used to detect the morphology of EVs-PLA microspheres and EVs. The release test detected the release behavior of EVs in EVs-PLA microspheres. Scanning electron microscopy was used to detect the morphological changes of EVs-PLA microspheres at 8 weeks of release. EVs-PLA microspheres were co-cultured with hepatocytes, and Phalloidin/DAPI staining was used to observe the cell morphology and evaluate the cytotoxicity of the microspheres. CCK8-test was used to evaluate the cell proliferation activity. Western blot analysis was used to detect extracellular vesicles membrane marker protein expression. Results Comparing the ability of hepatocyte proliferation in the group treated with EVs-PLA microspheres and the control group, it was found that EVs-PLA microspheres did not cause cell apoptosis and mutation in cell structure, had biocompatibility and no cytotoxicity. The EVs-PLA microspheres with "core-shell" structure regulated the release behavior of EVs, which can continuously release EVs, exerting a continuous biological role in promoting hepatocyte proliferation after a single intervention. Conclusions The EVs-PLA microspheres can control-release EVs and promote hepatocyte proliferation continuously after a single intervention, providing a reference for further exploration of EVs-loaded delivery systems in promoting liver regeneration.

Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Optimization of Gabapentin Release and Targeting Absorption, Through Incorporation into Alginate Beads.

Aims: 1) To study the effect of some formulation variables on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release. 2) Optimize the mucoadhesion capabilities for targeting drug absorption and release-controlling capabilities of alginate beads. Methodology: Alginate beads were prepared by dripping sodium alginate gel into calcium chloride solution and then dried overnight at ambient temperature. The effects of alginate concentration, cross linker concentration, cross linking time, volume of cross linking solution and drug/polymer ratio on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release were investigated. Formulae containing sodium lauryl sulfate (SLS), gabapentin-ethylcellulose solid dispersion, mixture of free drug and solid dispersion were prepared for modifying the drug release rate. Results: Mucoadhesion of alginate beads was shown to be decreased upon adding SLS (30% after 8 hrs). Drug release was so fast (92.46% after 2 hrs). The incorporation of solid dispersion has led to well accepted mucoadhesion (74.44% after 8 hrs) as well as release properties (93.35% after 10 hrs) Beads containing mixtures of drug and ethylcellulose-drug solid dispersion showed acceptable mucoadhesion (74.44% after 8 hrs) and control of gabapentin release (93.35% after 10 hrs). Statistical analysis of variance between groups was performed using the one-way layout ANOVA with duplication. Significant differences in mean values were evaluated by Student's unpaired t test (P < 0.05). Conclusion: A finally optimized formula was suggested by incorporating a combination of solid dispersion and free gabapentin in alginate system to achieve burst release of gabapentin and hence fast effect (33.417% was released during the first 30 minutes in fasting-simulated conditions) and controlled release (91.217% after 6 hrs).