Biomedical subjects

Sudaxshina Murdan

Publications and source records attributed to Sudaxshina Murdan.

9 recordsLinked to original sources

PubMed2006

Amphiphilogels as drug carriers: effects of drug incorporation on the gel and on the active drug.

Amphiphilogels (a subset of organogels) are being studied as drug carriers in our laboratories. In this paper, the effects of drug incorporation on the drugs and the gels are discussed. Amphiphilogels were prepared by heating a mixture of the gelator (sorbitan monostearate or sorbitan monopalmitate) and the liquid (e.g. Tweens or liquid Spans) to form a solution/dispersion, which was cooled to the gel state. Drugs were dissolved by heating a mixture of the drug and the gel and cooling the resulting solution. Hydrophilic gels (composed of hydrophilic Tweens as the liquid) were more effective solvents than hydrophobic ones (composed of hydrophobic Span 20 or 80 liquids). The latter's solvent capacity could, however, be increased by the inclusion of co-solvents, such as propylene glycol and ethanol. Drug incorporation at 10% w/w did not cause any detrimental changes in gel stability, while the drug's release rate was dependent on its concentration and on the nature of the gel's liquid component (which influences drug solubility), but not on gelator concentration or on the method of drug incorporation. This study shows the importance of the nature of the gels' liquid component and the possibility of using hydrophilic amphiphilogels as solvents for poorly water-soluble drugs.

Acetaminophen↗

PubMed2006

An investigation into the adjuvanticity and immunogenicity of zein microspheres being researched as drug and vaccine carriers.

We have determined whether zein microspheres could act as vaccine adjuvants i.e. increase the immune responses to co-administered immunogens. Ovalbumin (model antigen)-loaded zein microspheres, blank zein microspheres and ovalbumin solution were intramuscularly administered to mice and the sera antibody levels were determined by ELISA. Another group of mice was orally dosed with blank zein microspheres, and serum and faecal antibody levels were determined. As expected, negligible antibody titres were obtained with the ovalbumin solution. Surprisingly, intramuscular administrations of blank zein microspheres elicited high levels of serum IgG which bound to the ovalbumin antigen coated on ELISA microtitre plates. This indicated that anti-zein antibodies had been elicited by blank zein microspheres and that these antibodies were cross-reacting with ovalbumin antigen coated onto ELISA plates. Such cross-reactivity inhibited the determination of the adjuvant activity of zein microspheres, if any. Additional ELISA assays, where zein was used as the coating antigen, confirmed the generation of anti-zein antibodies by blank zein microspheres i.e. zein microspheres were immunogenic following intramuscular administration. Upon oral administration of blank zein microspheres, serum IgG levels remained low but intestinal IgA levels increased following booster doses i.e. systemic tolerance, but not mucosal tolerance, to oral zein particles was achieved. Zein microspheres were immunogenic when administered intramuscularly and orally.

Administration, Oral↗

PubMed2005

Novel gels and their dispersions--oral drug delivery systems for ciclosporin.

Amphiphilogels (gels that consist solely of surfactants) and gel-based emulsion (GEM) formulations (solutions that gel upon incorporation of small amounts of water) were investigated as oral delivery vehicles for ciclosporin A, in in vivo experiments in Beagle dogs. Both systems represent essentially self-dispersing non-lipidic drug delivery systems based on amphiphilic surfactants. Three different amphiphilogels (hydrophobic, hydrophilic and hydrophilic gel containing ethanol), the aqueous dispersions of the latter two amphiphilogels and of two GEM formulations were tested to determine the influence of (i) gel hydrophilicity/hydrophobicity, (ii) presence of ethanol, (iii) pre-dispersion of gels into aqueous medium prior to oral administration and (iv) size of dispersions, on drug absorption. It was found that all the formulations tested, except for the hydrophilic amphiphilogel and its aqueous dispersion, were bioequivalent to Neoral, the commercially available preparation. High drug absorption from the bioequivalent formulations was thought to be due to the fact that following oral administration, ciclosporin remained in a soluble form, hence was available for absorption, despite relatively large droplet sizes of the formulations. The hydrophilic gel and its dispersion allowed less drug absorption; this was assigned to the fact that, when the hydrophilic amphiphilogel contacted an aqueous medium, there were no lipophilic domains in which the drug could remain soluble. It is possible that some drug precipitated out and was unavailable for absorption.

Absorption↗

PubMed2005

Organogels in drug delivery.

In the last decade, interest in physical organogels has grown rapidly with the discovery and synthesis of a very large number of diverse molecules, which can gel organic solvents at low concentrations. The gelator molecules immobilise large volumes of liquid following their self-assembly into a variety of aggregates such as rods, tubules, fibres and platelets. The many interesting properties of these gels, such as their thermoreversibility, have led to much excitement over their industrial applications. However, only a few organogels are currently being studied as drug/vaccine delivery vehicles as most of the existing organogels are composed of pharmaceutically unacceptable organic liquids and/or unacceptable/untested gelators. In this paper a brief overview of organogels is presented, followed by a more in-depth review of the gels that have been investigated for drug and/or vaccine delivery. These include microemulsion-based gels and lecithin gels (studied for transdermal delivery), sorbitan monostearate organogels and amphiphilogels (studied as vaccine adjuvants and for oral and transdermal drug delivery, respectively), gels composed of alanine derivatives (investigated as in situ forming gels) and Eudragit organogels (studied as a matrix for suppositories). Finally, pluronic lecithin organogels, descendents of lecithin gels but which are not really organogels, are briefly discussed for their interesting history, their root and the wide interest in these systems.

Drug Carriers↗

PubMed2004

In vivo investigation, in mice and in man, into the irritation potential of novel amphiphilogels being studied as transdermal drug carriers.

Amphiphilogels, gels that consist solely of non-ionic surfactants, are being developed as dermal/transdermal drug delivery vehicles in our laboratories. The irritation potential of two amphiphilogels was investigated on shaved mouse skin, in vivo, and compared to those of Aqueous Cream BP (a moisturiser) and 5% sodium lauryl sulphate (SLS) solution (a known irritant). The skin irritation potential of one of these gels was then investigated in human, using Aqueous Cream BP as a negative control. Skin irritation (following daily application of gels and of controls for 5 days) was assessed by laser Doppler velocimetry, a visual erythema scoring method, and histological evaluations of excised mice skin. We found that the amphiphilogels caused no significant increase in blood flow and in epidermal irritation. In contrast, the SLS solution caused significant perturbation to mouse skin. From this study we conclude that these amphiphilogels may be used as dermal/transdermal drug delivery vehicles.

Administration, Cutaneous↗

PubMed2004

Amphiphilogels for drug delivery: formulation and characterization.

PURPOSE: This study examines the microstructure, gelation temperatures, and flow properties of novel amphiphilogels consisting solely of non-ionic surfactants. METHODS: Gels were prepared by mixing the solid gelator (sorbitan monostearate or sorbitan monopalmitate) and the liquid phase (liquid sorbitan esters or polysorbates) and heating them at 60 degrees C to form a clear isotropic sol phase, and cooling the sol phase to form an opaque semisolid at room temperature. Gel microstructure was examined by light and electron microscopy and by small angle neutron scattering (SANS); gelation temperatures were measured by hotstage microscopy, a melting point apparatus, and high sensitivity differential scanning calorimetry (HSDSC). Flow rheograms were performed to establish the zero-rate viscosity of the gels and their performance under shear. RESULTS: Gel microstructures consisted mainly of clusters of tubules of gelator molecules that had aggregated upon cooling of the sol phase, forming a 3D network throughout the continuous phase. The gels demonstrated thermoreversibility. Gelation temperature and viscosity increased with increasing gelator concentration, indicating a more robust gel network. At temperatures near the skin surface temperature, the gels softened considerably; this would allow topical application. CONCLUSIONS: This study has demonstrated the formation/preparation of stable, thermoreversible, thixtropic surfactant gels (amphiphilogels) with suitable physical properties for topical use.

Administration, Topical↗

PubMed2003

Electro-responsive drug delivery from hydrogels.

Precise control over the release of drug from devices implanted in the body, such as quantity, timing, is highly desirable in order to optimise drug therapy. In this paper, the research on electrically-responsive drug delivery is reviewed. Electrically-controllable drug release from polyelectrolyte hydrogels has been demonstrated in vitro and in vivo (in rats). Pulsatile drug release profiles, in response to alternating application and removal of the electric field have been achieved. Responsive drug release from hydrogels results from the electro-induced changes in the gels, which may deswell, swell or erode in response to an electric field. The mechanisms of drug release include ejection of the drug from the gel as the fluid phase synereses out, drug diffusion along a concentration gradient, electrophoresis of charged drugs towards an oppositely charged electrode and liberation of the entrapped drug as the gel complex erodes. Electrically-responsive drug release is influenced by a number of factors such as the nature of the drug and of the gel, the experimental set-up, magnitude of the electric field etc. In this paper, electrically-responsive hydrogels, response of gels to an electric field and electrically-stimulated drug release are discussed.

Delayed-Action Preparations↗

PubMed2002

Drug delivery to the nail following topical application.

The absorption of drugs into the nail unit, following topical application to the nail plate, is highly desirable to treat nail disorders, such as onychomycosis (fungal infections of the nail). Nail permeability is however quite low and limits topical therapy to early/mild disease states. In this paper, the recent research into ungual drug delivery is reviewed. The nail unit and the two most common diseases affecting the nail--onychomycosis and nail psoriasis--are briefly described to set the scene and to give an overview of the nature and scope of the problem. The factors, which affect drug uptake and permeation through the nail plate such as solute molecular size, hydrophilicity/hydrophobicity, charge, and the nature of the vehicle, are then discussed, followed by ways of enhancing drug transport into and through the nail plate. Finally, drug-containing nail lacquers which, like cosmetic varnish, are brushed onto the nail plates to form a film, and from which drug is released and penetrates into the nail, are reviewed.

Administration, Topical↗

PubMed2002

Loading into and electro-stimulated release of peptides and proteins from chondroitin 4-sulphate hydrogels.

Chondroitin 4-sulphate (CS) hydrogels were examined as potential matrices for the electro-controlled delivery of peptides and proteins. A CS hydrogel, cross-linked with ethylene glycol diglycidyl ether, and with a swelling ratio of 20, was used to study the influence of molecular size and shape of guest molecules on loading and release rates. Three positively charged molecules of different molecular weights (vasopressin MW 1084, aprotinin MW 6512 and lysozyme MW 14,400), and one negatively charged protein (bovine serum albumin MW 67,000) were used as model solutes. The hydrogels were loaded by equilibrium swelling. As a result, the three positively charged peptide and proteins were found to be concentrated in the gels, most likely due to ionic attraction between the negative charges in the gel polymeric backbone and the positively charged solutes. No such concentration of solute in the gel was seen for the negatively charged albumin. The latter is presumably loaded passively by diffusing in the water phase of the gel. The loading efficiency (indicated by the loading rate and the total amount of solute loaded in the gel) was found to increase with decreasing molecular size of solute. Electro-stimulated release of the loaded peptide and proteins was followed for 3 h during which an electric field was applied in pulses of 5 V (pulse duration and pulse interval were both of 20 min). The release of lysozyme and aprotinin from CS hydrogels responded to electrical pulses. On the other hand, vasopressin and albumin were largely released by passive diffusion and their release could not be electrically controlled. This work shows that the size of the guest molecule is an important parameter when electrically-stimulated drug release is desired, but further work obviously needs to be carried out with a larger range of molecular weights and conformations.

Aprotinin↗