Augmented Anticancer Effects of Cantharidin with Liposomal Encapsulation: In Vitro and In Vivo Evaluation.

PEGylated liposomes have received much attention as pharmaceutical carriers to deliver chemotherapeutic agents for therapeutic purpose. The aim of this study was to prepare and characterize PEGylated liposome of cantharidin and investigate its therapeutic effect on human hepatocellular carcinoma treatment in vitro and in vivo. Liposomal cantharidin was evaluated for their anticancer effects in vitro using human hepatocellular carcinoma HepG2 cells and in vivo using HepG2-bearing nude mice compared to free drug. PEGylated liposome of cantharidin had a particle size of 129.9 nm and a high encapsulation efficacy of approximately 88.9%. The liposomal cantharidin had a higher anti-proliferative effect vis-à-vis free cantharidin in inducing G2/M cell cycle arrest and apoptosis. Liposomal cantharidin killed more HepG2 cancer cells at the same concentration equivalent to free cantharidin. Further study in vivo also showed that liposomal cantharidin achieved a higher tumor growth inhibition efficacy than free drug on hepatocellular carcinoma. As our study exhibited enhanced cytotoxicity against HepG2 cells and augmented tumor inhibitory effects in vivo, the results validate the potential value of cantharidin-liposome in improving the therapeutic efficacy of cantharidin for liver cancer.

Development of liposomal salbutamol sulfate dry powder inhaler formulation.

The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.

Evolution of transmaxillary approach to tumors in pterygopalatine fossa and infratemporal fossa: anatomic simulation and clinical practice.

BACKGROUND: The endoscopic transnasal approach has been proven to have advantages on the removal of the tumors in pterygopalatine fossa (PPF) and infratemporal fossa (ITF). Herein, this study aimed to describe a modified approach for resection of the tumors in these areas, both in cadaveric specimen and clinical patients. METHODS: The 20 adult cadaveric specimens and five patients with tumors in PPF and ITF were enrolled in this study. For the cadaveric specimens, ten were simulated anterior transmaxillary approach and ten were performed modified endoscopic transnasal transmaxillary approach. The exposure areas were compared between two groups and main anatomic structure were measured. Surgery was operated in the five patients with tumors of PPF and ITF to verify the experience from the anatomy. Perioperative management, intraoperative findings and postoperative complications were recorded and analyzed. RESULTS: The modified endoscopic transnasal transmaxillary approach provided as enough surgical exposure and high operability to the PPF and ITF as the anterior transmaxillary approach did. The diameter of maxillary artery in the PPF was 3.77 ±â€Š0.78 mm (range: 2.06-4.82 mm), the diameter of middle meningeal artery in the ITF was 2.79 ±â€Š0.61 mm (range: 1.54-3.78 mm). Four patients who suffered schwannoma got total removal and one of adenocystic carcinoma got subtotal removal. The main complications were facial numbness and pericoronitis of the wisdom tooth. No permanent complication was found. CONCLUSIONS: With the widespread use of neuroendoscopy, the modified endoscopic transnasal transmaxillary approach is feasible and effective for the resection of tumors located in PPF and ITF, which has significant advantages on less trauma and complications to the patients.

[Responses of neurons and astrocytes in rat hippocampus to kainic acid-induced seizures].

OBJECTIVE: To investigate the time course of the responses of neurons and astrocytes in rat hippocampus (HI) to kainic acid (KA)-induced seizures in various regions. METHODS: By means immunohistochemical staining for anti-Fos protein and anti-glial fibrillary acidic protein (GFAP), the regional distribution of reactive neurons and astrocytes in the HI was observed at different time points after a unilateral stereotaxic microinjection of KA into the lateral ventricle of rats to cause limbic and generalized convulsive seizures. RESULTS: The injection of KA triggered limbic motor seizures including immobilization, staring, facial and jaw clonus ect. followed by recurrent generalized convulsive seizures. After KA-induced seizures, the GFAP-positive astrocytes and Fos-positive neurons were markedly increased in the HI. The increase of GFAP immunoreactivity was observed 30 min after the seizure onset, reaching the maximum at 1 h; the increase of Fos immunoreactivity was detected at 1 h after the onset, peaking at 2 h. CONCLUSION: The neurons and astrocytes in rat HI are highly active during seizures and the reactive astrocytes might play an important role in epileptogenesis.

Novel ophthalmic timolol meleate liposomal-hydrogel and its improved local glaucomatous therapeutic effect in vivo.

To overcome the limitations of common eye drops, the study developed a novel timolol mealate (TM) liposomal-hydrogel to enhance drug permeability and prolong residence time in the precorneal region, which achieved more effective local glaucomatous therapeutic effect. Firstly, TM liposome was prepared by an ammonium sulfate gradient-pH regulation method, which its entrapment efficiency reached up to 94% and its averaged particle size is 187 nm with narrow distribution. The corneal permeability through isolated rabbit cornea was measured by modified Franz-type diffusion cells. The results of trans-corneal penetration exhibited that the apparent permeability coefficients (P(app)) and the flow rates of steady state (J(ss)) of TM liposome was 1.50-fold higher than that of the commercialized eye drop, while TM liposome with 0.02% transcutol P was 2.19 times. In order to increase the retention time and improve the stability of liposome, we further developed a TM liposomal-hydrogel formulation by adding 1.0% HPMC K4M in TM liposome. The results showed an stability during a 120 days storage period than TM liposome. Precorneal retention study in vivo indicated that the optimal liposomal-hydrogel formulation had improved bioavailability and its retention time on rabbit corneal surface were significantly longer than that of pure liposomes or eye-drops. No obvious irritations to rabbit eyes were observed by histopathology microscopy after 7 days exposure.. Comparing to the eye drops, the TM liposomal-gel displayed prolonged therapeutic effect in cornea and greatly lowered the intraocular pressure IOP on the eyes of normal and glaucomatous pigmented rabbits.