Increasing Cellular Uptake and Permeation of Curcumin Using a Novel Polymer-Surfactant Formulation.

Several therapeutically active molecules are poorly water-soluble, thereby creating a challenge for pharmaceutical scientists to develop an active solution for their oral drug delivery. This study aimed to investigate the potential for novel polymer-surfactant-based formulations (designated A and B) to improve the solubility and permeability of curcumin. A solubility study and characterization studies (FTIR, DSC and XRD) were conducted for the various formulations.

An evaluation of the adhesion of solid oral dosage form coatings to the oesophagus.

There is a requirement for the development of oral dosage forms that are adhesive and allow extended oesophageal residence time for localised therapies, or are non-adhesive for ease of swallowing. This study provides an initial assessment of the in vitro oesophageal retention characteristics of several widely utilised pharmaceutical coating materials. To this end, a previously described apparatus has been used to measure the force required to pull a coated disc-shaped model tablet across a section of excised oesophageal tissue.

An in vitro model for the evaluation of the adhesion of solid oral dosage forms to the oesophagus.

Adhesion of solid oral dosage forms to the oesophagus can be a disadvantage when delivering drugs that may cause oesophageal damage, or can be an advantage when developing localised therapies for this region. In this study, apparatus to investigate coatings that may influence oesophageal retention was developed and evaluated. The apparatus incorporated a section of porcine oesophageal mucosa held flat by the application of a gentle vacuum and kept moist by the application of a simulated saliva solution.

Nasal and buccal drug delivery: management forum conference.

The scope of the conference (Nasal and Buccal Drug Delivery Conference, Management Forum; Chairs Franz Merkus and Julie Suman) was to consider innovations in drug delivery via the nose and oral cavity, notably for the delivery of vaccines, antimalarials and rapidly acting sedatives. Presentations from experts from academia, government agencies and commercial organisations were made over the 2 days. The advantages of both routes were ease of application, patient acceptability and no requirement to produce sterile products.

Chitosan microparticles for the controlled delivery of fluoride.

Objectives: To manufacture and characterise chitosan/fluoride microparticles prepared by spray drying and assess their utility as controlled release vehicles for fluoride.

Methods: Microparticles were manufactured from dispersions containing 1.0% and 2.

Metabolism of captopril carboxyl ester derivatives for percutaneous absorption.

Objectives: To determine the metabolism of captopril n-carboxyl derivatives and how this may impact on their use as transdermal prodrugs. The pharmacological activity of the ester derivatives was also characterised in order to compare the angiotensin converting enzyme inhibitory potency of the derivatives compared with the parent drug, captopril.

Methods: The metabolism rates of the ester derivatives were determined in vitro (using porcine liver esterase and porcine ear skin) and in silico (using molecular modelling to investigate the potential to predict metabolism).

Azo compounds in colon-specific drug delivery.

Azo compounds have the potential to act as drug carriers that facilitate the selective release of therapeutic agents to the colon, and also to effect the oral administration of those macromolecular drugs that require colon-specific drug delivery. With some further research-driven refinements, these materials may lead to more efficient treatments for local conditions, such as colonic cancer or inflammatory bowel disease. This article provides an overview of the azo-based systems developed to date, identifies the requirements for an ideal carrier, and highlights the directions for further developments in the field of azo group-facilitated colonic delivery.

Orally administered, colon-specific mucoadhesive azopolymer particles for the treatment of inflammatory bowel disease: An in vivo study.

Radiolabeled congeners of a series of azopolymers have been synthesized and characterized. The in vivo (rat) gastrointestinal transit profile of millimeter-sized particles of these azopolymers has been determined and used to facilitate the selection of a candidate material for therapeutic applications. The efficacy of the selected material as a protective coating for the colonic mucosa has been tested in a hapten-reactivated, in vivo model of inflammatory bowel disease: 7 days after reactivation of the condition, the myeloperoxidase activity of animals that had received doses of the selected azopolymer was determined to be at the same level as that of healthy animals or that of the negative control group, highlighting the therapeutic promise of this material.

Design, synthesis and characterization of captopril prodrugs for enhanced percutaneous absorption.

Most drugs are designed primarily for oral administration, but the activity and stability profiles desirable for this route often make them unsuitable for transdermal delivery. We were therefore interested in designing analogues of captopril, a model drug with poor percutaneous penetration, for which the sustained steady-state blood plasma level associated with transdermal delivery (and which is unattainable orally) would be particularly beneficial. Quantitative structure-permeability relationships (QSPRs) predicted that ester and thiol prodrug derivatives of captopril would have lower maximal transdermal flux (J(m)) than the parent drug, since the increases in permeability coefficient (k(p)) of prodrugs would be outweighed by the reductions in aqueous solubility.

Buccal drug delivery.

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured.

The basics and underlying mechanisms of mucoadhesion.

Mucoadhesion is where two surfaces, one of which is a mucous membrane, adhere to each other. This has been of interest in the pharmaceutical sciences in order to enhance localised drug delivery, or to deliver 'difficult' molecules (proteins and oligonucleotides) into the systemic circulation. Mucoadhesive materials are hydrophilic macromolecules containing numerous hydrogen bond forming groups, the carbomers and chitosans being two well-known examples.

Recent developments in the use of bioadhesive systems for delivery of drugs to the oral cavity.

The delivery of therapeutic agents to, or via, the oral cavity is limited by the efficient removal mechanisms that exist in this area. Bioadhesive formulations have been developed to allow prolonged localized therapy and enhanced systemic delivery. The oral mucosa however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for "biopharmaceutical" products arising from the recent innovations in genomics and proteomics.

Mucoadhesive, triclosan-loaded polymer microspheres for application to the oral cavity: preparation and controlled release characteristics.

The aim of this study was to develop mucoadhesive microspheres that can be utilised for the controlled release of triclosan in oral-care formulations, specifically dental pastes. Using a double-emulsion solvent evaporation technique, triclosan was incorporated into microspheres that were prepared from Gantreztrade mark MS-955, Carbopol 974P, polycarbophil or chitosan and the profiles for its release were established under simulated 'in use' conditions. Triclosan was rapidly released into a sodium lauryl sulphate containing buffer from all but the chitosan microspheres.

In situ evaluation of drug-loaded microspheres on a mucosal surface under dynamic test conditions.

The ability of polymeric microspheres fabricated from Carbopol, polycarbophil, chitosan or Gantrez to retain a model hydrophilic drug (sodium fluorescein) was evaluated in situ, using a dynamic test system and image analysis. This technique used oesophageal tissues and simulated the physiological conditions within the oral cavity in terms of temperature, humidity and saliva flow. The point of sample application was observed over a 2h period by means of a digital camera.

Lectin-mediated drug delivery in the oral cavity.

The delivery of therapeutic agents to, or via, the oral cavity is limited by the efficient removal mechanisms that exist in this area. Lectins are proteins or glycoproteins that bind to specific sugar residues, and can, therefore, interact with the glycoconjugates present on cell surfaces or salivary mucins. Endogenous lectins could also be used as points of attachment for carbohydrate-containing delivery systems.

The retention of 14C-labelled poly(acrylic acids) on gastric and oesophageal mucosa: an in vitro study.

Polymers that bind from solution onto gastric mucosa can be used either as a means of facilitating localised drug delivery, or can act as therapeutic agents in their own right (e.g. by forming a protective layer or by inhibiting enzymes).

Mucin/poly(acrylic acid) interactions: a spectroscopic investigation of mucoadhesion.

Studies using infrared, (1)H and (13)C nuclear magnetic resonance, and X-ray photoelectron spectroscopies and differential scanning calorimetry support the hypothesis that hydrogen bonds, formed between the carboxylic acid functionality of the mucoadhesive material poly(acrylic acid) and the glycoprotein component of mucus, play a significant role in the process of mucoadhesion. There are fewer H-bonded interactions between the components than within the bulk of the pure mucoadhesive agent. The pH of the medium influences the structures of both the poly(acrylic acid) and the mucus, which, in turn, determine the nature and the extent of mucoadhesive interactions.

Polymeric microspheres for drug delivery to the oral cavity: an in vitro evaluation of mucoadhesive potential.

Polymeric microparticles were fabricated from Carbopol, polycarbophil, chitosan, or Gantrez using a "water-in-oil emulsification" solvent evaporation method. Mean particle sizes, as determined by laser diffraction, were in the range 23-38 microm. Electron microscopy revealed that all microparticles were spherical and of smooth surface morphology.

Adsorbed pluronics on the skin of human volunteers: effects on bacterial adhesion.

An amphiphilic copolymer, Pluronic F127, has been deposited, by adsorption, to the skin of human volunteers and the ability of the coated skin to resist bacterial colonisation has been evaluated. In parallel, the ability of the same copolymer to act as a bacterial release agent has been evaluated. In both cases, F127 proved to be of little added value in formulations designed to suppress the bacterial colonisation of human skin.

Adsorbed poly(ethyleneoxide)-poly(propyleneoxide) copolymers on synthetic surfaces: spectroscopy and microscopy of polymer structures and effects on adhesion of skin-borne bacteria.

Poly(ethyleneoxide)-copoly(propyleneoxide) (PEO-PPO) polymer coatings were evaluated for their resistance to the attachment of the marker organism Serratia marcescens and the skin-borne bacteria Staphylococcus epidermidis. The copolymers were adsorbed onto poly(styrene) films-chosen as simplified physicochemical models of skin surfaces-and their surface characteristics probed by contact angle goniometry, attenuated total reflectance-Fourier transform infrared (ATR-FTIR), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). These functional surfaces were then presented to microbial cultures, bacterial attachment was assessed by fluorescence microscopy and AFM, and the structures of the polymer films examined again spectroscopically.

A quantitative evaluation of radiolabelled lectin retention on oral mucosa in vitro and in vivo.

Previous work has identified lectins that bind to the cells present on the oral mucosa for their potential use as a means of retaining a drug delivery system on the mucosal surfaces of the mouth. In this study, a radiolabelling technique was developed to allow the quantification of lectin binding to human buccal cells in vitro, and the retention of the lectins in the oral cavity of a rat model in vivo. Lectins were labelled with 99mTc using a cyclic diethylene triamine pentaacetic acid conjugation technique.

An in vitro model for investigating the gastric mucosal retention of 14C-labelled poly(acrylic acid) dispersions.

Polymers that bind from solution onto gastric mucosae can be used as a means of facilitating localised drug delivery, or act as therapeutic agents in their own right (e.g. by forming a protective layer or by inhibiting enzymes).