Comparison of albumin and casein microspheres as a carrier for doxorubicin.

Doxorubicin (Adriamycin)-loaded casein and albumin microspheres, with diameters between 14 and 38 micron (50% weight average) were prepared by glutaraldehyde stabilization of the aqueous phase (containing protein and drug) of a water in oil emulsion. Physical properties, drug loading characteristics and release rates from microspheres in-vitro have been compared and correlated with effects on tumour growth when injected intratumourally in rats. Compared with albumin, the surface charge of the casein system was more negative and the microspheres exhibited a slower release of drug in-vitro.

Characterization of in-vitro drug release and biological activity of methotrexate-bovine serum albumin conjugates.

Two series of methotrexate (MTX)-bovine serum albumin (BSA) conjugates have been prepared containing either 96 +/- 16 mg (mean +/- s.d.) or 32 +/- 13 mg of MTX per gram of conjugate.

Adriamycin-loaded niosomes: drug entrapment, stability and release.

The effect of encapsulation of adriamycin into niosomes, and its resultant chemical purity, was studied by means of HPLC and high-speed scanning spectrophotometry (the simultaneous use of which allowed investigation of potential non-fluorescent drug degradation products), and the process shown not to adversely affect the drug. Efficiency of entrapment of aqueous solutions of the drug was apparently dependent on neither vesicle composition nor method of production, and evidence of a degree of surfactant-adriamycin association was provided by the high entrapment values. Light-induced drug degradation was reduced by niosome encapsulation, and efflux of entrapped adriamycin was decreased by inclusion of cholesterol into the vesicles, in a manner similar to that reported for liposome preparations.

The effect of the non-ionic surfactant Brij 30 on the cytotoxicity of adriamycin in monolayer, spheroid and clonogenic culture systems.

The effects of a non-ionic polyoxyethylated lauryl ether surfactant (Brij 30) on monolayer uptake and spheroid penetration of adriamycin have been studied. Co-incubation of adriamycin with Brij 30 increases intracellular adriamycin levels by 2-3-fold. Although, in the concentrations used, Brij 30 alone is not cytotoxic, adriamycin and Brij 30 mixtures are significantly more cytotoxic (monolayer ID90 = 0.

The nature of the oil phase and the release of solutes from multiple (w/o/w) emulsions.

The effect of the nature of the oil phase of w/o/w emulsions stabilized by interfacial complexation between span 80 (sorbitan mono-oleate) and albumin has been studied. The long-term stability of the systems has been assessed by photomicrography and by measuring the quantity of an internal marker (NaCl) remaining entrapped with time. The number of multiple oil drops and the diameters of the internal aqueous droplets were determined over 6 weeks, and the amounts of NaCl entrapped over the same period were followed.

Skin reflectance measurements of patch test responses.

Skin reflectance values were used as an objective measure of skin haemoglobin content at patch test sites to facilitate quantification of the erythematous response to contact allergens in patients with allergic contact dermatitis. Reflectance measurements of patch test responses correlated well with the clinical scoring and provided a numerical measure of reaction severity. Experimental contact allergen formulations were also evaluated by this method.

The effect of niosomes and polysorbate 80 on the metabolism and excretion of methotrexate in the mouse.

The effect of non-ionic surfactant vesicle (niosome) encapsulation on the metabolism and urinary and faecal excretion of methotrexate (MTX) in mice has been studied following oral and intravenous administration, and compared with the effects of co-administration of free drug and polysorbate 80, which does not form vesicles. Niosome entrapment reduces the excretion of MTX into urine and bile whereas polysorbate 80 increases its excretion. Monitoring of the levels of MTX and its 7-hydroxy metabolite indicates that entrapped MTX is protected from rapid metabolism in vivo, particularly in niosomes but to a small degree in the micellar systems formed by polysorbate.

The preparation and properties of niosomes--non-ionic surfactant vesicles.

Vesicles were prepared on hydration of a mixture of a single or double alkyl-chain, non-ionic surfactant with cholesterol. These vesicles, or 'niosomes', are capable of entrapping and retaining water soluble solutes such as carboxyfluorescein, are osmotically active and can be formulated to release entrapped solute slowly. The physical characteristics of the vesicles were found to be dependent on the method of production and three such methods, based on liposome technology, are described.

Application of emulsion theory to complex and real systems.

Synopsis Theories of emulsion stability are discussed in relation to dilute, concentrated and semisolid emulsions. It is shown that whilst a unified theory cannot be applied quantitatively to emulsion systems, a better understanding of the various mechanisms of stabilization and breakdown is emerging. Established concepts, eg, the HLB concept, are now given a less empirical gloss.

In vitro release of adriamycin from drug-loaded albumin and haemoglobin microspheres.

Release of adriamycin from albumin and haemoglobin microspheres has been determined in vitro using a flow through system. Release from cross-linked albumin microspheres is controlled by the percentage of glutaraldehyde used but release profiles of spheres of 23, 41 and 60 microns diameter were virtually superimposable. Not all of the adriamycin is released from the microspheres over 20 h; as biodegradation occurs in vivo after 24 h the amount of drug remaining in the system at 20 h is likely to be principally released by degradation of the protein matrix in vivo.

Vecuronium in the myasthenic patient.

The use of vecuronium in six patients with myasthenia gravis undergoing thymectomy is described the train-of-four twitch technique was used to monitor neuromuscular function. The first two patients received an initial dose of 0.02 mg/kg and incremental doses of 4 micrograms/kg, which is in the order of one fifth of that normally used.

Patch testing for nickel allergy. The influence of the vehicle on the response rate to topical nickel sulphate.

A group of 43 patients with a clinical history of nickel allergy who exhibited an equivocal or no allergic reaction to a patch test at 48 h were further challenged using several different formulations of nickel sulphate. This experimental test battery comprised aqueous, dimethyl sulphoxide (DMSO) and propylene glycol (PG) solutions of nickel sulphate, and nickel sulphate incorporated into cetomacrogol cream and yellow soft paraffin (PMF). Although some of these vehicles were irritant, a formulation-dependent test response was observed, such that in terms of the number of responses per unit weight of nickel sulphate applied to the skin, the vehicles could be ranked: DMSO greater than PG greater than aqueous solution greater than cetomacrogol cream greater than PMF preparations.

The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice.

Non-ionic surfactant vesicles (niosomes) prepared from a non-ionic surfactant, cholesterol and dicetyl phosphate and containing methotrexate (MTX) have been administered to mice. Given intravenously the niosomes prolong the levels of MTX in the blood, large amounts of the drug being taken up by the liver. There was also an increased uptake of MTX into the brain, perhaps due to an effect of the niosome components on the permeability of the blood brain barrier.

A low density lipoprotein-methotrexate covalent complex and its activity against L1210 cells in vitro.

Low-density lipoprotein particles are potential drug carriers, but only lipophilic drug species partition into the core of the system. In this paper the polar drug methotrexate has been coupled to the exterior protein of low density lipoprotein (LDL) particles using the reagent 1-ethyl-3(3'-dimethylaminopropyl) carbodiimide HCl. The coupled system was sized by photon correlation spectroscopy and the in vitro activity of the complex determined against L1210 cells maintained in medium supplemented with fetal calf serum.

The distribution and elimination of methotrexate in mouse blood and brain after concurrent administration of polysorbate 80.

This paper describes further exploration of the effect of polysorbate 80 on the absorption, distribution, and elimination of methotrexate (MTX). This study has confirmed the earlier finding that polysorbate 80 could increase the absorption of MTX from the mouse gastrointestinal tract and enhance the drugs uptake into the brain. The experiments reported here suggest that polysorbate 80 has a direct effect on the blood-brain barrier leading to the increased uptake of MTX, which is evident following IV administration.

Adriamycin-loaded albumin microspheres: preparation, in vivo distribution and release in the rat.

Adriamycin-loaded bovine albumin microspheres have been prepared by a technique that allows preparation and administration to animals on the same day. Criteria adopted for injection were that microspheres should be stable and of a size such as to become trapped in capillary beds. These conditions were fulfilled by preparing microspheres using glutaraldehyde concentrations greater than 0.

Atracurium in the myasthenic patient.

The use of the new competitive muscle relaxant, atracurium, is described in five myasthenic patients presenting for thymectomy. With an initial dose of 0.1 mg/kg, that is approximately one-fifth of that normally used, and incremental doses of 0.

Anaesthesia for transcervical thymectomy in myasthenia gravis.

A modified technique of total intravenous anaesthesia was used in the management of 22 patients with myasthenia gravis of varying severity undergoing therapeutic transcervical thymectomy. The relatively short-acting intravenous hypnotics, Althesin and etomidate were compared for induction of anaesthesia and for maintenance as a supplement to 50% nitrous oxide in oxygen. Moderately high doses (20 or 25 micrograms/kg) of the potent, synthetic opiate, fentanyl provided analgesia and a level of respiratory depression sufficient to facilitate control of respiration.

Cervical thymectomy in the treatment of myasthenia gravis.

A retrospective review of 22 patients undergoing cervical thymectomy for myasthenia gravis is presented. Their ages ranged from 19 to 67 years. The male and female ratio as well as the severity of illness prior to operation were similar to other reported series.

Interactions of ionic and non-ionic surfactants with plasma low density lipoprotein.

Surfactants might be useful in facilitating the replacement of the interior of low density lipoprotein (LDL2) (p = 1.02-1.063 g ml-1) with drug molecules.

Medication problems of rheumatic patients assessed by domicillary visits by pharmacists.

A pilot scheme of domicillary visits to thirty-three rheumatic patients attending either a specialized clinic or general practitioners was undertaken. Patients' understanding of their therapy and compliance with prescribed regimens was assessed, and a comparison made between specialized medical records and actual medications found in the home. A number of cases are discussed in detail to highlight some of the problems uncovered.

Stabilization of water/oil/water multiple emulsions by polymerization of the aqueous phases.

In order to improve the stability of w/o/w multiple emulsions which have isopropyl myristate as the non-aqueous 'oil' phase, either the internal aqueous phase of the multiple system or the secondary (outer or continuous) aqueous phase can be gelled. Production, by gamma-irradiation, or cross-linked polyacrylamide or poloxamer gels in the aqueous phases of the emulsions leads to systems which have a greater intrinsic stability than untreated multiple emulsions. If the internal aqueous phase is gelled this prevents coalescence.

Effects of polysorbate 80 on the absorption and distribution of oral methotrexate (MTX) in mice.

This study is part of a programme of work aimed at improving the bioavailability of oral methotrexate (MTX). In preliminary experiments no significant effect of non-ionic surfactant polysorbate 80 (Tween 80) on absorption of 0.5 mg MTX X kg-1 in NMRI mice was observed except when the drug was given together with 6% polysorbate 80 in solution.

Non-ionic surfactants and gastric mucosal transport of paraquat.

The influence of a range of polyoxyethylated non-ionic surfactants upon the transport of [14C]-paraquat dichloride across rabbit isolated gastric mucosa was investigated. Paraquat was shown to cross the mucosal epithelium by passive diffusion. Certain members of the surfactant series enhanced transmucosal paraquat transfer at low surfactant concentrations (e.

Grazing cow and calf responses to zinc supplementation.

This experiment evaluated weight gain responses to supplemental Zn by cows and calves grazing forage containing less than 20 ppm Zn. One hundred cow-calf pairs in each of 2 years and 120 paird in a third year were pastured together over a 63- to 77-day preliminary period during which cows were exposed to bulls. Each experimental period began in mid-June after bulls were removed and continued for 125 to 154 days.