New biocompatible hydroxy double salts and their drug delivery properties

Two biocompatible hydroxy double salts (HDSs) were synthesised for the first time and loaded with active pharmaceutical ingredients. Drug release was studied from these intercalates, and sustained release observed. The HDS–drug composites were further formulated into tablets which were found to comply with pharmacopeia requirements for delayed and extended release dosage forms

Hydroxy double salts loaded with bioactive ions: Synthesis, intercalation mechanisms, and functional performance

The intercalation of the anions of diclofenac (Dic), naproxen (Nap), and valproic acid (Val) into three hydroxy double salts (HDSs) has been explored in this work. Experiments were performed with [Co1.2Zn3.8(OH)8](NO3)2·2H2O (CoZn-NO3), [Ni2Zn3(OH)8](NO3)2·2H2O (NiZn-NO3) and [Zn5(OH)8](NO3)2·2H2O (Zn-NO3). It proved possible to intercalate diclofenac and naproxen into all three HDSs. In contrast, Val could be intercalated into CoZn-NO3 but when it was reacted with Zn-NO3 the HDS structure was destroyed, and the product comprised ZnO. Successful intercalation was verified by X-ray diffraction, IR spectroscopy, and elemental microanalysis. Molecular dynamics simulations showed the Dic and Nap ions to arrange themselves in an “X” shape in the interlayer space, forming a bilayer. Val was found to adopt a position with its aliphatic groups parallel to the HDS layer, again in a bilayer. In situ time resolved X-ray diffraction experiments revealed that intercalation of Dic and Nap into CoZn-NO3 and Zn-NO3 is mechanistically complex, with a number of intermediate phases observed. In contrast, the intercalation of all three guests into NiZn-NO3 and of Val into CoZn-NO3 are simple one step reactions proceeding directly from the starting material to the product. The HDS-drug composites were found to have sustained release profiles

Combined In Situ and In Silico Studies of Guest Intercalation into the Layered Double Hydroxide [LiAl2(OH)(6)]X•yH2O

Phosphonoacetate (PAA), diethyl phosphonoacetate (DPA), and sulfoacetate (SAA) anions have been intercalated into the galleries of the layered double hydroxide (LDH) [LiAl2(OH)6·X]·yH2O (LiAl-X; X = Cl, NO3). X-ray diffraction (XRD), Fourier transform infrared spectroscopy, and elemental microanalysis confirmed the successful intercalation of the guest ions into the LDH. The guests could also be de-intercalated and recovered from the host intact. In situ XRD was used to probe the mechanisms of the reactions, and the intercalation of PAA proceeded via clear intermediate phases. In contrast, the SAA and DPA reactions did not show any intermediates, but the organic intercalates exhibited changes in their interlayer spacing as the reaction progressed. Molecular dynamics (MD) simulations were used to investigate the interlayer structure of the intercalation compounds. It was found that the intermediates observed in situ correspond to local energy minima in the MD simulations. MD can thus predict the course of an intercalation reaction and allow the a priori identification of intermediate phases. This is the first time that in silico and in situ measurements have been combined to unravel this level of understanding of intercalation reactions

Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model

<p>Abstract</p> <p>Background</p> <p>Fully covered Self-Expanding metal stents (FCSEMS) have been shown efficacious in palliating malignant biliary obstructions. There is little data analyzing mucosal response to their temporary placement in the bile duct.</p> <p>Methods</p> <p>Ten mini pigs underwent endoscopic placement of a FCSEMS (Wallflex, Boston Scientific). FCSEMS were kept in place for three months. At the end of the 3 months, FCSEMS were removed endoscopically. Five pigs were euthanized and their bile ducts harvested. The other five were kept alive for another month post removal. A single pathologist, created a scoring system (to determine degree of inflammation, fibrosis, and epithelial injury), examined all specimens in a blinded fashion.</p> <p>Results</p> <p>Four FCSEMS spontaneously migrated in the duodenum. On post mortem examination, mild mucosal thickness was noted in three bile duct specimens while superficial inflammation of the bile duct was noted in five animals. Histologic examination of the bile duct revealed focal acute inflammation in both groups. For the 5 animals euthanized immediately after stent removal, there was a tendency to have superficial mucosal erosion and fibrosis. In contrast, increased chronic inflammation was more commonly seen in the animals 1 month post stent removal, with all animals in this group showing moderate degrees of mononuclear inflammatory cell mucosal infiltrates. No severe inflammatory or fibrotic duct injury was observed in any of the study animals, with degree of injury graded as mild to moderate.</p> <p>Conclusion</p> <p>FCSEMS appear to induce minimal tissue overgrowth or fibrosis post placement. Ease of removability and no significant histologic injury are advantages noted with FCSEMS., however, further studies are needed to evaluate treating benign biliary strictures with FCSEMS in humans.</p

Stenting and interventional radiology for obstructive jaundice in patients with unresectable biliary tract carcinomas

Together with biliary drainage, which is an appropriate procedure for unresectable biliary cancer, biliary stent placement is used to improve symptoms associated with jaundice. Owing to investigations comparing percutaneous transhepatic biliary drainage (PTBD), surgical drainage, and endoscopic drainage, many types of stents are now available that can be placed endoscopically. The stents used are classified roughly as plastic stents and metal stents. Compared with plastic stents, metal stents are of large diameter, and have long-term patency (although they are expensive). For this reason, the use of metal stents is preferred for patients who are expected to survive for more than 6 months, whereas for patients who are likely to survive for less than 6 months, the use of plastic stents is not considered to be improper. Obstruction in a metal stent is caused by a tumor that grows within the stent through the mesh interstices. To overcome such problems, a covered metal stent was developed, and these stents are now used in patients with malignant distal biliary obstruction. However, this type of stent has been reported to have several shortcomings, such as being associated with the development of acute cholecystitis and stent migration. In spite of these shortcomings, evidence is expected to demonstrate its superiority over other types of stent

Systematic review for non-surgical interventions for the management of late radiation proctitis

Chronic radiation proctitis produces a range of clinical symptoms for which there is currently no recommended standard management. The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation proctitis and evaluate the evidence for their efficacy. Synonyms for radiation therapy and for the spectrum of lower gastrointestinal radiation toxicity were combined in an extensive search strategy and applied to a range of databases. The included studies were those that involved interventions for the non-surgical management of late radiation proctitis. Sixty-three studies were identified that met the inclusion criteria, including six randomised controlled trials that described the effects of anti-inflammatory agents in combination, rectal steroids alone, rectal sucralfate, short chain fatty acid enemas and different types of thermal therapy. However, these studies could not be compared. If the management of late radiation proctitis is to become evidence based, then, in view of its episodic and variable nature, placebo controlled studies need to be conducted to clarify which therapeutic options should be recommended. From the current data, although certain interventions look promising and may be effective, one small or modest sized study, even if well-conducted, is insufficient to implement changes in practice. In order to increase recruitment to trials, a national register of cases with established late radiation toxicity would facilitate multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected