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Stanley S Davis

Publications and source records attributed to Stanley S Davis.

4 recordsLinked to original sources

Absorption enhancers for nasal drug delivery.

This paper describes the basic concepts for the transmucosal delivery of drugs, and in particular the use of the nasal route for delivery of challenging drugs such as polar low-molecular-weight drugs and peptides and proteins. Strategies for the exploitation of absorption enhancers for the improvement of nasal delivery are discussed, including consideration of mechanisms of action and the correlation between toxic effect and absorption enhancement. Selected enhancer systems, such as cyclodextrins, phospholipids, bioadhesive powder systems and chitosan, are discussed in detail. Examples of the use of these enhancers in preclinical and clinical studies are given. Methods for assessing irritancy and damage to the nasal membrane from the use of absorption enhancers are also described. Finally, the mucosal use of absorption enhancers (chitosan) for the improved nasal delivery of vaccines is reported with reference to recent phase I/II clinical studies.

Absorption↗

Parenteral polymers.

Explore the source record for details and available documents.

Drug Delivery Systems↗

The effect of ileal brake activators on the oral bioavailability of atenolol in man.

A study was carried out in human volunteers to investigate whether ileal brake activators could alter the bioavailability of atenolol from the small intestine by slowing intestinal transit and thereby increasing the time available for absorption. Oleic acid and a monoglyceride were formulated into modified release capsules that were targeted to the small intestine. Atenolol was either dosed separately or incorporated into one of the capsules. Radiolabelled non-disintegrating tablets were dosed at the same time in order to determine the small intestinal transit time (SITT). Plasma concentrations of atenolol were determined by HPLC. The results showed that in some volunteers an increase in SITT did lead to an increase in the quantity of drug absorbed. However, drug absorption was related not only to the total time spent by the drug in the small intestine but other factors such as the proportion of such time spent at the ileocaecal junction. The study highlights the complexities of exploiting natural gastrointestinal processes to enhance the oral bioavailability of drugs.

Administration, Oral↗

Development of multicomponent DNA delivery systems based upon poly(amidoamine)-PEG co-polymers.

PEGylated polyamidoamine (PAA) polymers were investigated for the production of sterically stabilised DNA delivery systems. Comparison of a PEGylated polymer (NG47) with a non-PEGylated polymer (NG49) showed similar binding of co-polymer to DNA by displacement of ethidium bromide (EB) and DNA melting studies. Gel electrophoresis, turbidimetric analysis and PCS demonstrated differences in the colloidal properties of the complexes, which were attributable to the formation of soluble complexes by the PEGylated co-polymer. However, transmission electron microscopy (TEM) showed that the resulting complexes containing poly(ethylene glycol) (PEG) were not well condensed, susceptible to degradation by nucleases, and thus not suited for in vivo delivery. The poor properties of the PEGylated co-polymer were attributed to an excess of PEG. However, polymer blends of NG47 and NG49 at defined ratios of polymer to co-polymer and total repeating units (RUs) to nucleotide, spontaneously formed complexes with a range of desirable properties. These included small size and polydispersity, high particle density, low surface charge and resistance to nuclease degradation. Complexes made with PEGylated polymer alone, and the polymer blends both suffered from a reduced polyfection activity. This was attributed to a low surface charge on the complex, which reduced interactions with the cell membrane and consequent uptake of the particles into the cell.

Animals↗