Hongxing Fu

Phospholipid-based ultrasonic microbubbles for loading protein and ultrasound-triggered release

Background: Ultrasonic microbubbles are used as ultrasound-triggered delivery carriers for protein drugs. Aim: This work was to prepare stabilized protein-loaded phospholipid-based ultrasonic microbubbles (PUM) and to determine its value as a protein delivery system. Method: Bovine serum albumin (BSA) was used as a model protein drug. BSA-containing PUM were prepared by dissolving lyophilized PUM powder in BSA solution. The particle size and microbubble concentration of BSA-containing PUM were measured. The BSA encapsulation efficiency as a function of BSA concentration was determined. Contrast enhancement of BSA-containing PUM in vivo was detected. The release profile of BSA from PUM was also investigated. Results: The mean particle size and microbubble concentration of PUM were unchanged by the presence of BSA for at least 30 minutes after preparation. The net amount of BSA entrapped in PUM was maintained unchanged with increasing BSA concentration. BSA-containing PUM were shown easily to be visible in in vivo rabbit kidney. There was no difference in echogenicity between the loaded and unloaded PUM. Ultrasound duration had a positive relationship with BSA release. Ultrasound of 30 seconds stimulated 94.1% and 93.3% of BSA release from PUM solutions containing 0.3% and 1.5% BSA, respectively. Conclusions: Protein-loaded PUM exhibited satisfactory physical characteristics and were potent for using in ultrasound-triggered delivery.

Experiment on formulation and drug release behavior of porosity asymmetric membrane capsules in vitro

Porosity asymmetric membrane capsules were prepared to study the relationship between the capsule formulation and drug release. Cellulose acetate (CA) and pore formers were used in the capsule shell formulation as the main semipermeable membrane material. The capsules were permeable to both water and dissolved solutes. Using sparingly soluble drug acetaminophen as a model, cumulative release was calculated. The slope of the release profile from the distilled water had good relationship with the concentration of the pore formers F68. The release of acetaminophen was independent to the pH, osmotic pressure of dissolution medium, but influenced by intensity of agitation. When the concentration of pore former was low, zero-order release behavior was observed within 24 h which was consistent with Fickian diffusion model. When the concentration of pore former was high, however, Higuchi model release was found which is caused by Fickian diffusion and osmotic pressure release. With scanning electron microscope (SEM), the surface structure and cross-section of the capsule shell were also studied before and after drug delivery. With simple preparation and broad scope of drug application, porosity asymmetric membrane capsules can give desired drug extended release and show more convenience than controlled tablets with laser drilling.

Preparation and antitumor activity of bFGF-mediated active targeting doxorubicin microbubbles.

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE–PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 μm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.

Comparing the Enhancement Efficiency Between Liposomes and Microbubbles for Insulin Pulmonary Absorption

BACKGROUND The present study investigated the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption. METHODS Two types of phospholipid-based vesicle-liposomes and microbubbles-were prepared, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity test was used to evaluate their in vitro toxicity in A549 cells. Cellular uptake of insulin combined with liposomes or microbubbles was determined using A549 cells. With intratracheal insufflation of Sprague-Dawley rats, an insulin mixture with liposomes or microbubbles was administered to assess its potential for promoting drug pulmonary absorption. RESULTS Both liposomes and microbubbles had a narrow and monodispersed size distribution with average diameter of 3.1 μm and 1.0 μm, respectively. From the MTT cytotoxicity test, a phospholipid-based vesicle concentration of <25% (vol/vol) in the final volume was the safe dosage range that could avoid severe cytotoxic effects. The intracellular uptake amount of insulin in the insulin-microbubble mixture was significantly higher than that in the insulin-liposome mixture. The minimum reductions of the blood glucose concentration produced by insulin-microbubble and insulin-liposome mixtures were 60.8% and 35.0% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.6% and 30.8%, respectively. CONCLUSIONS Microbubbles have much better efficiency than liposomes in the rate and extent of insulin pulmonary absorption. Microbubbles might be recommended as a potential agent for enhancing protein intrapulmonary absorption.