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.

Formulation and characterization of a captopril ethyl ester drug-in-adhesive-type patch for percutaneous absorption.

Background: The ethyl ester of captopril has been shown to exhibit enhanced permeation across human skin compared to the parent drug. A drug-in-adhesive patch formulation of a captopril ethyl ester was therefore developed for optimum drug release.

Method: A wide range of transdermal patches were prepared using two commercially available bioadhesive polymers.

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).

Renin-angiotensin-system gene polymorphisms and depression.

Given the abundance of the renin-angiotensin system (RAS) components in the brain, their importance in behavior and cognition, and the data that implicates them in the etiology and treatment of depression, it is possible that those RAS gene polymorphisms associated with increased RAS activity may also be associated with depression. The frequencies of common polymorphisms of genes encoding for components of the RAS, namely angiotensinogen (M235T), angiotensin converting enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C), and angiotensin receptor type II (C3123A) were determined in DNA extracted from buccal cells from a Lebanese population of 132 depressed patients and their first-degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC genotype was significantly associated with depression (p=0.

A potential anti-implantation and spermicidal strategy: putative derivatives of nonoxynol-9 and anti-inflammatory agents and their spermicidal activity.

Objectives: We report the synthesis of novel ester derivatives of nonoxynol-9, an approved spermicidal agent, using the non-steroidal inflammatory drugs (NSAIDs) ibuprofen and indomethacin. Indomethacin has previously been shown to inhibit the implantation of the fertilised ovum into the uterus wall of pregnant rats. It is proposed that nonoxynol-9, in combination with a non-selective NSAID may exhibit both anti-implantation and spermicidal properties.

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.

Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin.

Two common non-steroidal anti-inflammatory drugs (NSAIDs) and their nitric oxide (NO) adducts were evaluated for effects on stomach and thymus. Following 4-h duration (acute) oral dosing of fasted male Wistar rats, 1.33 x 10(-4)mol/kg of ibuprofen caused significant visual irritation score and microscopic thinning, although an ulceration assay proved insensitive.

Synthesis and spermicidal activity of a putative nitric oxide-releasing derivative of nonoxynol-9.

Objectives: We report on the synthesis of a potential nitric oxide releasing derivative of nonoxynol-9 (N9).

Methods: This derivative was synthesised via AgNO3 mediated nitroxylation of a chloride derivative of a N9 which itself was synthesised by thionyl chloride mediated chlorination of N9. In an initial in vitro study the spermicidal efficacy of the nitric oxide derivative and the parent compound (N9) was examined using boar spermatozoa.

A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity.

Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job's method.