Insulin-loaded liposomes packaged in alginate hydrogels promote the oral bioavailability of insulin.

Compared to subcutaneous injections, oral administration of insulin would be a preferred route of drug administration for diabetic patients. For oral delivery, both liposomes and alginate hydrogels face many challenges, including early burst release of the encapsulated drug and poor intestinal drug absorption. Also, adhesion to the intestinal mucosa remains weak, which all result in a low bioavailability of the payload. This study reports on an alginate hydrogel loaded with liposomes for oral insulin administration. Liposomes (Lip) loaded with arginine-insulin complexes (AINS) were incorporated into a hydrogel prepared from cysteine modified alginate (Cys-Alg) to form liposome-in-alginate hydrogels (AINS-Lip-Gel). An ex vivo study proves that intestinal permeation of AINS and AINS-Lip is approximately 2.0 and 6.0-fold, respectively, higher than that of free insulin. The hydrogel retarded early release of insulin (∼30%) from the liposomes and enhanced the intestinal mucosal retention. In vivo experiments revealed that the AINS-Lip-Gel released insulin in a controlled manner and possessed strong hypoglycemic effects. We conclude that liposome-in-alginate hydrogels loaded with AINS represent an attractive strategy for the oral delivery of insulin.

Development and analysis of machine-learning guided flash nanoprecipitation (FNP) for continuous chitosan nanoparticles production.

Chitosan-based nanoparticles (CNPs) are widely used in drug delivery, cosmetics formulation and food applications. To accelerate the manufacturing of CNPs, the present study develops a workflow to prepare CNPs in a continuous model. Based on machine learning, the workflow precisely predicts size and polymer dispersity index (PDI) value of CNPs, which impacts on the colloidal stability and applications. Multi-inlet vortex mixer (MIVM) device was fabricated by 3D printing as the reactor. Peristaltic pump was applied to deliver the reaction streams into the MIVM device and produce CNPs by flash nanoprecipitation (FNP) in a continuous way. The developed MIVM device produces CNPs in a controlled manner at a higher output which is promising for upscale applications. Twelve machine learning algorithms were employed to investigate the potential relationship between the reaction independent variables and hydrodynamic characteristics of CNPs. Random Forest, Decision Tree, Extra Tree and Bagging algorithms performed better than other algorithms with the average prediction accuracy around 90 %. The current study demonstrated that supervised machine learning guided FNP using the developed MIVM device is an effective strategy for accurate and intelligent production of CNPs and other similar nanoparticles.

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.

Enhancement of Curcumin Solubility by Phase Change from Crystalline to Amorphous in Cur-TPGS Nanosuspension.

Nanosuspensions (NSs) were fabricated to enhance water solubility, dissolution rate, and oral adsorption of water insoluble curcumin using sonoprecipitation method. As a good stabilizer, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) was used to improve the stability of curcumin-TPGS NSs (Cur-TPGS NSs). Ultrasonic homogenization (UH) could effectively enhance the solubility of curcumin and to produce homogeneous NSs with small particle sizes. Water solubility of curcumin was significantly improved from 0.6 µg/mL in pure water to 260 µg/mL in the mixture of curcumin and TPGS (1:10) with UH treatment. The mean particle size of Cur-TPGS NSs was decreased significantly after UH and maintained between 208 and 246 nm. Lyophilized powder of Cur-TPGS NSs was dissolved about 91.08% whereas the pristine curcumin powder was dissolved only 6.5% at pH 7.4. This study showed a great potential of Cur-TPGS NSs as a good nano-formulation of curcumin with enhanced solubility and improved oral adsorption.

Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin.

Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route.

Evaluation of the small intestinal submucosa covered stent in preventing restenosis after percutaneous transluminal angioplasty in the swine.

OBJECTIVE: To compare the performance of small intestinal submucosa (SIS)-covered endografts (SCEs) to bare nitinol stents (BSs) in injured swine iliac arteries. MATERIALS AND METHODS: Twenty-eight nitinol stents were used: 14 externally SCEs and 14 BSs. Devices were implanted in each side of balloon-injured external iliac arteries of 14 swine via carotid approach. Arteriograms were obtained before and after implantation and before animal sacrifice at 4, 8, and 12 weeks. Histopathological and electron microscopy studies of explanted specimens were performed. RESULTS: Implantation of all SCEs and BSs was technically successful, but one SCE and one BS were obstructed at 8 weeks after implantation. At sacrifice, the other 26 stents were patent, with angiogram showing no significant different luminal narrowing between SCEs and BSs. Proliferating cell nuclear antigen (PCNA) immunohistochemistry examination revealed that the percentage of PCNA(+) cells were lower in SCEs (p<0.05). Additionally, histomorphological analysis indicated that the neointima area and percentage of narrowing area were greater in SCEs, but there was no statistical significance. Greater endothelial cell count in SCEs than in BSs per visual field at 4000 times magnification by scanning electron microscope (p<0.05). CONCLUSION: Compared to BSs, no definite decrease of neointima and restenosis was found in SCEs in the present study. However, it is effective in promoting endothelial regeneration and strengthening endothelial function.