Lipid, sugar and liposaccharide based delivery systems

Although there are formidable barriers to the oral delivery of biologically active drugs, considerable progress in the field has been made, using both physical and chemical strategies of absorption enhancement. A possible method to enhance oral absorption is to exploit the phenomenon of lipophilic modification and mono and oligosaccharide conjugation. Depending on the uptake mechanism targeted, different modifications can be employed. To target passive diffusion, lipid modification has been used, whereas the targeting of sugar transport systems has been achieved through drugs conjugated with sugars. These drug delivery units can be specifically tailored to transport a wide variety of poorly absorbed drugs through the skin, and across the barriers that normally inhibit absorption from the gut or into the brain. The delivery system can be conjugated to the drug in such a way as to release the active compound after it has been absorbed (i.e. the drug becomes a prodrug), or to form a biologically stable and active molecule (i.e. the conjugate becomes a new drug moiety). Examples where lipid, sugar and lipid-sugar conjugates have resulted in enhanced drug delivery will be highlighted in this review.

Carbohydrate-based templates for synthetic vaccines and drug delivery

Methyl tetra-O-allyl, and tetra-O-[2-(tetrahydro-2H-pyranyl)oxy.-3-oxapentyl glucosides, and tetra-O-(cyanoethyl)galactosyl azide were converted into derivatives containing linkers with terminal carboxylic acid functionalities at the anomeric position and bearing four arms with phthaloyl- or BOC-protected terminal amino groups. These molecules were suitable for use in solid-phase peptide synthesis and for the preparation of dendrimers, containing multiple copies of peptides. (C) 2001 Elsevier Science Ltd. All rights reserved.

A Ku-band active transmit-array module with a horn or patch array as a signal launching/receiving device

This paper is concerned with the design of a Ku-band active transmit-array module of transistor amplifiers excited by either a pyramidal horn or a patch array Optimal distances between the active transmit array and the signal-launching:receiving device, which is either a passive corporate-fed array or a horn, are determined to maximise the power gain at a design frequency: Having established these conditions, the complete structure is investigated in terms of operational bandwidth and near-field and far-field distributions measured at the output side of the transmit array, The experimental results show that the use of a corporate-fed array as an illuminating/receiving device gives higher gain and significantly larger operational bandwidth, An explanation for this behavior is sought.

Fatal monensin toxicity in a dog after chewing a bovine intra-ruminal slow-release device

A 20kg, 10-month-old male Kelpie developed a rapid onset of profound paresis progressing to flaccid paralysis and dyspnoea, followed by death about 36 hours after chewing on a partly discharged anti-bloat capsule from a dead cow. Intoxication by monensin in the capsule was considered the cause of death. No Lodes holocyclus were found on the dog. Evidence of muscle damage was seen in clinical biochemistry assays of plasma, but consent for necropsy was not obtained. The median lethal dose for Beagle dogs of the material contained in anti-bloat capsules is 0.5-1.0g. As this represents a serious toxicity risk if dogs chew these devises, the manufacturer includes a warning on potential dog toxicity in product literature.

Parenteral and mucosal delivery of a novel multi-epitope M protein-based group A streptococcal vaccine construct: investigation of immunogenicity in mice

Primary vaccine strategies against group A streptococci (GAS) have focused on the M protein-the target of opsonic antibodies important for protective immunity. We have previously reported protection of mice against GAS infection following parenteral delivery of a multi-epitope vaccine construct, referred to as a heteropolymer. This current report has assessed mucosal (intranasal (i.n.) and oral) delivery of the heteropolymer in mice with regard to the induction and specificity of mucosal and systemic antibody responses, and compared this to parenteral delivery. GAS-specific IgA responses were detected in saliva and gut upon i.n. and oral delivery of the heteropolymer co-administered with cholera toxin B subunit, respectively. High titre serum IgG responses were elicited to the heteropolymer following all routes of delivery when administered with adjuvant. Moreover, as with parenteral delivery, serum IgG antibodies were detected to the individual heteropolymer peptides following i.n. but not oral delivery. These data support the potential of the i.n. route in the mucosal delivery of a GAS vaccine. (C) 2002 Elsevier Science Ltd. All rights reserved.

Ubiquitous travel service delivery

Free independent travelers require flexible, reactive service delivery due to their regularly changing location and activities and the lack of a wired Internet connection. A ubiquitous travel service delivery system that is able to dynamically deliver services in response to relevant events, such as changing location, availability of new last-minute specials, work opportunities, and safety issues can provide added value while retaining the flexibility that is so important to independent travelers. This article describes such a system. An engineering design research approach has been adopted to design the system. Issues addressed include traveler and service states and events, contexts, situations, and situation-action rules. An architecture is proposed that is based on distributed, cooperating software agents and mobile data technologies. The role of these agents is to continuously monitor situations that are occurring in the physical and virtual service spaces and to take the required action for any situations that are relevant to the traveler.

CRIM1 Regulates the Rate of Processing and Delivery of Bone Morphogenetic Proteins to the Cell Surface

The Crim1 gene is predicted to encode a transmembrane protein containing six von Willebrand-like cysteine-rich repeats (CRRs) similar to those in the BMP-binding antagonist Chordin (Chrd). In this study, we verify that CRIM1 is a glycosylated, Type I transmembrane protein and demonstrate that the extracellular CRR-containing domain can also be secreted, presumably via processing at the membrane. We have previously demonstrated Crim1 expression at sites consistent with an interaction with bone morphogenetic proteins (BMPs). Here we show that CRIM1 can interact with both BMP4 and BMP7 via the CRR-containing portion of the protein and in so doing acts as an antagonist in three ways. CRIM1 binding of BMP4 and -7 occurs when these proteins are co-expressed within the Golgi compartment of the cell and leads to (i) a reduction in the production and processing of preprotein to mature BMP, (ii) tethering of pre-BMP to the cell surface, and (iii) an effective reduction in the secretion of mature BMP. Functional antagonism was verified by examining the effect of coexpression of CRIM1 and BMP4 on metanephric explant culture. The presence of CRIM1 reduced the effective BMP4 concentration of the media, thereby acting as a BMP4 antagonist. Hence, CRIM1 modulates BMP activity by affecting its processing and delivery to the cell surface

In situ characterization of stickiness of sugar-rich foods using a linear actuator driven stickiness testing device

A stickiness testing device based on the probe tack test has been designed and tested. It was used to perform in situ characterization of drying hemispherical drops with an initial radius 3.5 mm. Tests were carried out in two drying temperatures, 63 and 95 degreesC. Moisture and temperature histories of the drying drops of fructose, honey, sucrose, maltodextrin and sucrose-maltodextrin mixtures were determined. The rates of moisture evaporation of the fructose solution was the fastest while those of the maltodextrin solution was the lowest. A profile reversal was observed when the temperature profiles of these materials were compared. Different modes of failure were observed during the stickiness tests. Pure fructose and honey solutions remained completely sticky and failed cohesively until the end of drying. Pure sucrose solution remained sticky and failed cohesively until complete crystallization occurred. The surface of the maltodextrin drops formed a skin shortly after the start of drying. It exhibited adhesive failure and reached a state of non-adhesion. Addition of maltodextrin significantly altered the stickiness of sucrose solution. (C) 2002 Elsevier Science Ltd. All rights reserved.