A comprehensive development strategy in buccal drug delivery.

This work combines several methods in an integrated strategy to develop a matrix for buccal administration. For this purpose, tablets containing selected mucoadhesive polymers loaded with a model drug (omeprazole), free or in a complexed form with cyclodextrins, and in the absence and presence of alkali agents were subjected to a battery of tests. Mucoadhesion studies, including simple factorial analysis, in vitro release studies with both model-dependent and model-independent analysis, and permeation studies were performed.

Hepatic and renal toxicities of indomethacin acid, salt form and complexed forms with hydroxypropyl-β-cyclodextrin on Wistar rats after oral administration.

Indomethacin (IM), a non-steroidal anti-inflammatory drug, has the capacity to induce hepatic and renal injuries when administrated systemically. The aim of this study is to assess the IM absorption from complexed forms when orally administered to rats, by means of a comparative evaluation of its capacity to induce hepatic and renal injury in different forms, namely IM acid, IM sodium salt or IM complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD), using freeze- and spray-drying methods. A total of 135 Wistar rats weighing 224.

Pharmacological effect of orally delivered insulin facilitated by multilayered stable nanoparticles.

Intestinal uptake, insulinemia and hypoglycemic effect of orally delivered insulin encapsulated in polyelectrolytically stable nanoparticles were evaluated in streptozotocin-induced Wistar diabetic rats. Nanoparticles with 396nm mean diameter were formed by alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin. The resulting negatively charged nanoparticles retained insulin bioactivity and enhanced pharmacological availability by shielding insulin from enzymatic degradation and through chemical and physical facilitation of permeation through the intestinal membrane.

Effects of galactose on direct and indirect pathway estimates of hepatic glycogen synthesis.

Hepatic glycogen is formed by direct and indirect pathways whose activities reflect altered nutrition or disease. Direct/indirect pathway measurements often involve test meals where ∼ 10% of carbohydrate is galactose, but its effects on direct/indirect pathway estimates are unknown. Therefore, direct/indirect pathway contributions in 24-h fasted rats given 2g/kg 100% glucose (GLU, n=6) or 90% glucose-10% galactose (GLU+GAL, n=6) were measured by [U-(13)C]glucose dilution and by position-5/position-2 glycogen enrichment (H5/H2) from 2H(2)O.

Assessment of the in-vivo drug release from pellets film-coated with a dispersion of high amylose starch and ethylcellulose for potential colon delivery.

Objectives: The aim of this study was to test the ability of a colon targeting system comprising pellets film-coated with a dispersion of high amylose starch (Hylon VII) and ethylcellulose (Surelease) (1 : 2 w/w) to deliver a model drug (5-aminosalicylic acid; 5-ASA) in vivo into the colon of rabbits. An uncoated pellet formulation was used as a control.

Methods: Six New Zealand female rabbits, approximately 2 kg, were randomly divided into two groups.

Interactions between DNA and nonionic ethylene oxide surfactants are predominantly repulsive.

In the present work, the interactions between double-stranded (ds) or single-stranded (ss) DNA and nonionic ethylene oxide (EO) surfactants, with special attention to the possible contributions from hydrophobic interactions, have been investigated using a multitechnique approach. It was found that the presence of ss as well as dsDNA induces a slight decrease of the cloud point of pentaethylene glycol monododecyl ether (C(12)E(5)). Assessment of the partitioning of DNA between the surfactant-rich and surfactant-poor phases formed above the cloud point showed that the polymer was preferably located in the surfactant-poor phase.

An investigation into the role of mucus thickness on mucoadhesion in the gastrointestinal tract of pig.

Mucoadhesion in the gastrointestinal tract is a complex phenomenon and both formulation and physiological features need to be well understood and considered. Mucus thickness has been inferred to play a role in this process; however no definitive influence has been established. This study aimed to investigate the influence of mucus thickness on the mucoadhesion process, using a large animal (pig) as a model to closely resemble the human physiological features.

Prevalence of high-grade squamous intraepithelial lesions and cervical cancer among patients with unsatisfactory colposcopic examination, without visible lesion.

Context And Objective: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL), the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment.

Combining strategies to optimize a gel formulation containing miconazole: the influence of modified cyclodextrin on textural properties and drug release.

Background: Miconazol, an antimycotic drug, is commonly formulated into semisolid formulations designed to be applied in the oral cavity to treat oral candidiasis. However, given its limited aqueous solubility, permeation through the biological membranes is low and therefore its activity is also limited. Cyclodextrins (CDs) have been widely used to increase the solubility and stability of poorly water-soluble drugs.

Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer.

Background: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment.

[Development and validation of the first Spanish questionnaire of quality of life in patients with prostate cancer, based on the patient's perception].

Background: To ensure health related quality of life (HRQOL) during the survival of patients with prostate cancer (PCa) is a priority. The development of specific HRQOL questionnaires aids to assess the disease impact, its treatment and the patient's perception (concerns, expectations and interests) that might go unnoticed.

Objectives: To develop and validate the first Spanish HRQL questionnaire specific for patients with PCa.

Influence of the coating formulation on enzymatic digestibility and drug release from 5-aminosalicylic acid pellets coated with mixtures of high-amylose starch and Surelease intended for colon-specific drug delivery.

Background: Colon-specific delivery of drugs can be achieved with dosage forms coated with biopolymers that are metabolized selectively by the colonic microflora and yet resistant to enzymatic digestion in the small intestine.

Aim: The aim of this study was to study the influence of formulation factors on the performance of mixed films from high-amylose starches and Surelease((R)), applied using a spray-coating process, as potential colon-specific delivery devices.

Methods: 5-Aminosalicylic acid-loaded pellets were prepared by an extrusion-spheronization process and film coated with mixtures of the starches and Surelease((R)).

Evaluation of gastric toxicity of indomethacin acid, salt form and complexed forms with hydroxypropyl-beta-cyclodextrin on Wistar rats: histopathologic analysis.

Indomethacin (IM) is a non-steroidal anti-inflammatory drug which inhibits prostaglandin biosynthesis. It is practically insoluble in water and has the capacity to induce gastric injury. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is an alkylated derivative of beta-CD with the capacity to form inclusion complexes with suitable molecules.

Hemicellulose dressing versus rayon dressing in the re-epithelialization of split-thickness skin graft donor sites: a multicenter study.

The aim of this study was to compare the effectiveness of a hemicellulose dressing with that of rayon dressing in the healing of split-thickness skin graft donor sites. Twenty-eight patients were selected from five different hospitals and randomized into two groups: hemicellulose dressing group and rayon dressing group. All patients underwent split-thickness skin grafting for various reasons, and the skin graft donor site wounds were covered with hemicellulose dressing (n=14) or rayon dressing (n=14).

Design for optimization of nanoparticles integrating biomaterials for orally dosed insulin.

Design of nanoparticles integrating biomaterials that govern the functional behavior of orally dosed insulin is focused on improving insulin stability and absorption by facilitating its uptake and translocation throughout the intestinal membrane, while providing protection from acidic and enzymatic degradation in the gastrointestinal tract. The purpose of the study was to optimize a nanoparticle formulation by investigating the relationship between design factors and experimental data by response surface methodology. Designed nanoparticles consisting of calcium crosslinked alginate, dextran sulfate, poloxamer 188 and chitosan followed by an outermost coating of albumin are described as multilayer complex retaining insulin within the nanoparticle.

Cellulose Dressing Versus Rayon Dressing in Skin Graft Donor Sites: Aspects of Patients' Health-related Quality of Life and Self-esteem .

Unlabelled:  Objective. The aim of this study was to compare the health-related quality of life (HRQoL) and self-esteem of patients who underwent split-thickness skin grafting, when either cellulose dressings or rayon dressings were applied to the donor sites.

Methods: A total of 25 patients, who were enrolled at five participant hospitals and required split-thickness skin grafting for various clinical reasons, were randomized into two treatment groups, the rayon dressing group (n = 13), or the cellulose dressing group (n = 12).

Percutaneous aortic valvuloplasty in inoperable symptomatic severe aortic stenosis in the very elderly.

Aortic valve replacement is the first therapeutic option in patients with symptomatic severe aortic stenosis. Given the fact that percutaneous aortic valve implantation is a relatively new procedure and the need for palliative treatment in symptomatic patients with a high surgical risk, percutaneous balloon aortic valvuloplasty is still employed. The authors describe two cases of percutaneous balloon aortic valvuloplasty in very elderly patients with severe calcified aortic stenosis not suitable for cardiac surgery, exacerbated in one case by significant coronary artery disease and left ventricular systolic dysfunction.

Colloidal carrier integrating biomaterials for oral insulin delivery: Influence of component formulation on physicochemical and biological parameters.

Strategies to design effective and safe colloidal carriers for biopharmaceuticals have evolved through applying the knowledge gained in nanotechnology to medicine. Designing a colloidal carrier to serve as a protein delivery device requires an understanding of the effect of different materials on the physicochemical, physiological and toxicological parameters for clinical application. The purpose of this study was to evaluate the influence of formulation components on the physicochemical factors and biological function involved in the development and optimization of newly designed nanoparticles for orally dosed insulin.

Starch-based coatings for colon-specific delivery. Part II: physicochemical properties and in vitro drug release from high amylose maize starch films.

This work reports an investigation into free-film properties of a high amylose maize starch-based film coating that has been used in the preparation of formulations for drug delivery to the colon (WO 2008/012573 A1) and relates these properties to in vitro drug release from pellets. Maize starch/ethylcellulose free films were prepared and characterised by scanning electron microscopy (SEM), light microscopy, modulated differential scanning calorimetry (mDSC), Fourier-transform infrared (FT-IR), X-ray and % swelling in aqueous fluids with pH conditions similar to the stomach and small intestine. 5-ASA release from film-coated pellets was tested in enzyme free simulated gastric fluid and phosphate buffer pH 7.

Starch-based coatings for colon-specific drug delivery. Part I: the influence of heat treatment on the physico-chemical properties of high amylose maize starches.

In this study, the changes in the physico-chemical properties of different high amylose maize starches, i.e., Hylon VII, Hylon V and IM-DS acetate starch, were studied prior and after heat treatment used in the preparation of film coatings (WO 2008/012573 A1).

Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-beta-cyclodextrin.

The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD) and 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) in aqueous solution by phase solubility studies. Inclusion complexes with MbetaCD in the solid state were then prepared by different methods, i.e.

Cervical stenosis following electrosurgical conization.

Context And Objective: Cervical stenosis is a postoperative complication of procedures for treating preinvasive lesions of the cervix and takes on particular importance due to the clinical repercussions associated with it. Furthermore, it causes limitations in relation to cytological and colposcopic follow-up. The aim here was to assess the incidence of cervical stenosis among a cohort of patients who underwent electrosurgical conization and to identify possible prognostic factors associated with its occurrence.

In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery.

In this work the enhancing effect of cyclodextrins on the buccal permeation of a hydrophobic model drug, omeprazole was studied. First, the influence of the complexation with cyclodextrins in the absence and in the presence of an alkali agent, L-arginine, on the drug stability was checked at neutral conditions since omeprazole alone is only stable in basic conditions. In vitro transbuccal permeation of omeprazole non-complexed and complexed with beta- and methyl-beta-cyclodextrin and in presence of L-arginine was examined using freshly obtained porcine buccal mucosa.

Strategies toward the improved oral delivery of insulin nanoparticles via gastrointestinal uptake and translocation.

The design of strategies that improve the absorption of insulin through the gastrointestinal tract is a considerable challenge in the pharmaceutical sciences and would significantly enhance the treatment of diabetes mellitus. Several strategies have been devised to overcome physiologic and morphologic barriers to insulin absorption, including the inhibition of acidic and enzymatic degradation, enhancement of membrane permeability or widening of tight junctions, chemical modification of insulin, and the formulation of carrier systems. In particular, the concept of nanoparticulate carriers for oral insulin delivery has evolved through remarkable advances in nanotechnology.