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The physical properties of biogels and their permeability for macromolecular drugs and colloidal drug carriers.

Macromolecular drugs, either free or complexed with colloidal drug carriers, have created a great deal of interest during the last decade. If one wants to administer these new therapeutics via the oral, nasal, and cervical routes or through the conductive airways, one of the first barriers to overcome is the mucus layer that adheres to the related epithelia. In this review, the physicochemical properties of biogels, macromolecular drugs, and colloidal drug carriers that play a major role in transport through biogels are reviewed. Also, methods of studying the mobility of macromolecular drugs and colloidal drug carriers in and through biogels are addressed.

Animals↗

A study of technetium-labelled sulphide colloid uptake by regional lymph nodes draining a tumour-bearing area.

With appropriate controls, experimental groups of inbred C3H mice bearing a syngeneic mammary carcinoma challenge in their right rear footpads were injected in both rear footpads with 99TcmASC. Mice were sacrificed 15 and 90 min after the labelled colloid injection. Popliteal and sacral lymph nodes were weighed and counted in a well scintillation counter. A marked inhibition of labelled colloid uptake was demonstrated in regional lymph nodes draining a tumour-bearing area. Rabbits bearing VX2 carcinoma in a forelimb received 99TcmASC into each front footpad. Depression of labelled colloid uptake by regional lymph nodes draining tumour was evident on gamma-camera scanning.

Animals↗

Colloid osmotic pressure and serum albumin following surgery.

The fall in serum albumin which occurs after operation can be modified by an intraoperative infusion of 20 g salt-poor human albumin, and the associated fall in colloid osmotic pressure is also corrected. There is a decrease in postoperative oliguria following a colloid infusion but no significant effect has been demonstrated on urinary sodium excretion. Th alteration of fluid and electrolyte metabolism after surgery does not appear to be a direct effect of lowered plasma colloid osmotic pressure. It is suggested that the effect of intraoperative albumin infusion is predominantly haemodynamic.

Albumins↗

Hen egg immunoglobulin Y in colloidal gold agglutination assay: comparison with rabbit immunoglobulin G.

Conjugation of immunoglobulin G (IgG) from rabbit serum with colloidal gold for sol agglutination assay was conducted. Effects of various buffer systems on conjugation and stability of sols were studied. Colloidal gold assay for detection of human myoglobin and C-reactive protein was developed. It was shown that rabbit IgG had a poor stabilizing effect on colloidal gold sol and therefore that it cannot be effectively used in such assays. In contrast, hen egg immunoglobulin Y (IgY) had excellent stabilizing properties used in various buffer systems and in a wide range of concentrations. IgY was considered as a useful alternative for rabbit antibodies in gold sol agglutination assay.

Agglutination Tests↗

Superoxide-mediated lysis of erythrocytes: the role of colloid-osmotic forces.

Although superoxide anions are a well-known mediator of cytotoxicity, their mechanism of target cell lysis is not clearly understood. In the present study we have used an exogenous source of superoxide to study erythrocyte cytolysis. RBC lysis was studied in buffers containing the cations Li+, Na+, K+, Rb+, and Cs+; superoxide anions were produced and available in these buffers. During this model superoxide-dependent cytolytic process, erythrocytes underwent a shape change from biconcave disk to sphere as shown by scanning electron microscopy. Soret band transmitted light microscopy has confirmed this shape change and shown that it precedes cytosolic oxidation. This evidence is consistent with a colloid-osmotic type lytic mechanism. Erythrocyte lysis was studied by 51Cr-release and light scattering methods. Superoxide-mediated target cytolysis was characterized by: 1) a sigmoidal dose-response curve and 2) a lag time in cytolysis after superoxide addition in kinetic light scattering experiments. The efficacy of cytolysis followed the rank order Cs+ > Rb+ > Na+, Li+ > sucrose = raffinose, which provides additional support for a colloid-osmotic lytic mechanism. Furthermore, the rank order potency correlates with the cations' hydration numbers. We suggest that oxidative events trigger the formation of colloid-osmotic pores approximately 1 nm in diameter.

Buffers↗

An autonomous phase-boundary detection technique for colloidal hard sphere suspension experiments.

Colloidal suspensions of monodisperse spheres are used as physical models of thermodynamic phase transitions and as precursors to photonic band gap materials. Current techniques for identifying the phase boundaries involve manually identifying the phase transitions, which is very tedious and time-consuming. In addition, current image analysis techniques are not able to distinguish between densely packed phases within conventional microscope images, which are mainly characterized by degrees of randomness or order with similar grayscale value properties. We have developed an intelligent machine vision technique that automatically identifies colloidal phase boundaries. The technique utilizes intelligent image processing algorithms that accurately identify and track phase changes vertically or horizontally for a sequence of colloidal hard sphere suspension images. This technique is readily adaptable to any imaging application wherein regions of interest are distinguished from the background by differing patterns of motion over time.

Algorithms↗

Separation and characterization of the colloidal phases produced on digestion of common formulation lipids and assessment of their impact on the apparent solubility of selected poorly water-soluble drugs.

Colloidal mixtures containing bile salts (BS), phosphatidylcholine (PC), and medium and long-chain monoglycerides and fatty acids were prepared as model systems to represent typical intestinal contents after digestion of formulation derived lipids under both low (5 mM BS/1.25 mM PC) and high (20 mM BS/5 mM PC) BS and PC conditions. Size-exclusion chromatography of the colloidal species that formed in the medium-chain digests indicated the presence of vesicles, mixed micelles, and simple micelles, whereas the long-chain digests contained only vesicles and mixed micelles. In the long-chain digests the mixed micellar phase was the predominant drug solubilizing species for griseofulvin, danazol, and halofantrine, although for increasingly lipophilic drugs, the vesicular phase contributed an increasing proportion of the solubilization capacity. In contrast, the solubilization capacity of the vesicular phase was predominant in the medium-chain digests, and no clear trends were evident in the relationship between drug lipophilicity and proportional solubilization. These data highlight the need to consider the colloidal species that form in the small intestine during the digestion of common formulation lipids and the coincident enhancement in drug solubilization provided under these circumstances.

Chemistry, Pharmaceutical↗

Microencapsulation of drugs with aqueous colloidal polymer dispersions.

Sustained-release polymer particles containing drugs with various solubility characteristics (ibuprofen, theophylline, guaifenesin, and pseudoephedrine HCl) were prepared with colloidal polymer dispersions in a completely aqueous environment as an alternative to conventional microencapsulation techniques, which use organic solvents. Spherical particles were prepared by spraying or dropping dilute sodium alginate solutions (0.67%, w/w) containing the dissolved or dispersed drug and colloidal polymer particles into calcium chloride solutions. The gelled particles, which formed by ionotropic gelation of the polysaccharide with calcium ions, were dried and cured at 60 degrees C to cause fusion of the colloidal polymer particles into a homogeneous matrix system. Actual drug contents close to 50% and encapsulation efficiencies of between 80 and 98% were achieved with all drugs. Guaifenesin and ibuprofen acted as plasticizers for the ethyl cellulose pseudolatex, whereas with theophylline and pseudoephedrine HCl, dibutyl sebacate had to be added as a plasticizer to yield a nondisintegrating polymer matrix. The stirring time before separation of the particles from the gelation medium had to be minimized with the water-soluble drugs to maximize drug loading; however, it was not critical with the water-insoluble drugs. Drug release was a function of the solubility of the drug, drug loading, and the type of polymer dispersion used.

Capsules↗

The biological fate of sulphur colloid.

The in-vivo behaviour of sulphur colloid has been investigated using colloids labelled with 35S as well as 99m Tc. The rates of clearance of 35S and 99m Tc from the blood, the rates of accumulation in liver and bone and the distribution of the two radioisotopes in various organs are all markedly different. The results demonstrate that although technetium is rapidly removed from the blood stream and primarily accumulated in the liver the colloid particles themselves are broken down in vivo with the release of sulphur.

Animals↗

Structure-function relationship in hemoproteins: the role of cytochrome c3 in the reduction of colloidal sulfur by sulfate-reducing bacteria.

Cytochromes c3 of different strains of sulfate-reducing bacteria have been purified and tested for their capacity to reduce colloidal sulfur to hydrogen sulfide. The results are in good agreement with the activities reported for the whole cells. Cytochrome c3 is the sulfur reductase of some strains of sulfate-reducing bacteria such as Desulfovibrio desulfuricans Norway 4 and sulfate-reducing bacterium strain 9974 from which the sulfur reductase activity can be purified with the cytochrome c3. In contrast, Desulfovibrio vulgaris Hildenborough cytochrome c3 is inhibited by the product of the reaction namely hydrogen sulfide. Chloramphenicol has no effect on the sulfur reductase activity of D. desulfuricans Norway 4 when resting cells grown on lactate-sulfate medium are put in the presence of colloidal sulfur. This shows that the sulfur reductase activity is constitutive and corresponds to the fact that colloidal sulfur grown cells do not contain more cytochrome c3 (or another sulfur reductase) than lactate-sulfate-grown cells.

Chloramphenicol↗

Silver-enhanced colloidal gold probes as markers for scanning electron microscopy.

Silver enlargement of small colloidal gold particles has been extensively used for the light microscopical visualization of gold probes. Very recently, a few investigators have employed physical developers in electron microscopy (both pre-embedding and on-grid staining methods). We now demonstrate that physical development of small colloidal gold particles advantageously can be exploited for labelling biological surfaces in scanning electron microscopy. This novel application of silver enhancement of colloidal gold particles is characterized by a high detection efficiency. Thus, specimens are labelled with small gold probes affording high immunocytochemical efficiency but being impossible to detect with the present scanning microscopes. These particles are subsequently scanning electronmicroscopically visualized by silver enhancement.

Animals↗

Fine-granular cationic iron colloid. Its preparation, physicochemical characteristics and histochemical use for the detection of ionized anionic groups.

In order to obtain distinct and reliable information concerning the localization of ionized anionic groups in tissues, fine-granular cationic ferric hydroxide colloid solution (Fe-Cac-f) was newly devised. This can be obtained by boiling a mixture of ferric chloride and ammonium cacodylate solutions. The colloid particles of Fe-Cac-f are about 1.0 nm in size, i.e., one-fifth of the size of ferric cacodylate colloid (Fe-Cac; Seno et al. 1983a). As with Fe-Cac, Fe-Cac-f particles in the pH range of 1.6-7.6 carry a positive electric charge, but the latter show a better permeation of tissues. Using the Prussian blue reaction, Fe-Cac-f gives a distinct deep-blue color and can be used for the detection of anionic groups of acid mucopolysaccharides and proteins by light microscopy. It is also useful for detecting the exact sites of ionized anionic groups in deep tissue areas using electron microscopy.

Animals↗

Primary actinomycoma of the third ventricle--the colloid cyst. A histochemical and ultrastructural study.

Primary actinomycoma of the third ventricle has been reported to be a very rare form of central nervous system actinomycosis. Others have demonstrated actinomycotic-like colonies in colloid cysts of the third ventricle. We have confirmed these structures (HLS) in five colloid cysts and have demonstrated by various histochemical stains that they consist of desoxyribose nucleic acid, base protein and phospholipid. Ultrastructurally, they consist of amorphous to granular electron dense material, probably deposited on a lamellar substructure. On the basis of the available information, we believe that the lesions, previously reported as primary actinomycomas, are actually colloid cysts containing degenerative HLS. The possible origin of the hyphal-like structures is discussed.

Actinomyces↗

[99mTc-sulfur-rhenium colloid and 111In-indium citrate in bone-marrow scintigraphy].

Bone marrow scinitigraphy using 111In-Indium-citrate and 99mTc-sulfur rhenium colloid was compared with each other in 6 male and 3 female patients. Our results in all patients were in favour of 111In-citrate which caused a better delineation of morphological details than 99mTc-sulfur rhenium colloid did. In the first days after intravenous administration of 111In-citrate, radioindium accumulated markedly in the pudendal region, this finding being more distinct in male patients than in female ones. On account of these results a considerable radiation dose has to be assumed in bone marrow scinitigraphy using 111In-citrate as long as the absorbed dose from 111In has not been estimated under consideration of the radioindium accumulation in the pudendal region. 111In-citrate should be applied in bone marrow scanning only exceptionally and 99mTc-sulfur rhenium colloid be preferred in the routine diagnostics of bone marrow.

Adult↗

Stereotactic endoscopic treatment of colloid cysts of the third ventricle.

In order to avoid invasive procedures (transfrontal, transcallosal) in the surgical treatment of colloid cysts the stereotactic aspiration technique was introduced by Bosch, Rähn and Backlund in 1978. The viscosity of the intracystic colloid and the displacement of the cyst away from the aspiration needle are possible reasons for unsuccessful aspiration. GT-guided stereotactic endoscopic technique gives the opportunity to fenestrate the cyst wall under direct visual control. After CT-guided stereotactic puncture of the right lateral ventricle with the foramen of Monro as target a steerable endoscope is introduced and the foramen of Monro is passed. The wall of the cyst is fenestrated and coagulated by means of monopolar (or laser) coagulation. Using this technique we have treated four patients with colloid cysts. Immediately postoperatively all of them were relieved of their complaints and have been symptom-free for a mean follow up period of twelve months. Studies of cerebrospinal fluid flow patterns, performed prior to and every six months after the endoscopic intervention, confirmed a remarkable reduction of foraminal obstruction.

Adult↗

Bovine pituitary intraglandular colloid fraction F5 localized in the rat endocrine pancreas.

Bovine pituitary intraglandular colloid thought to be a waste product, is the holocrine secretion of intermediate lobe cells. It is housed in the intraglandular lumen (residual lumen) and is extruded into the venous circulation of the cavernous sinuses via clefts in the capsule of the gland aligned with the intraglandular lumen. Intraglandular colloid, fraction F5 (mol.wt 34,000), radiolabeled with (125I)Na and injected (0.15 ml) into the right internal jugular vein of male Wistar rats, accumulated in the endocrine pancreas. Autoradiographs showed that the material had specifically localized in the capillary network of the endocrine pancreas. Since the intermediate lobe is poorly vascularized, intraglandular colloid is considered to be the transport medium for intermediate lobe materials.

Animals↗

Treatment of cholerheic diarrhea with cholestyramine and a hydrophilic colloid.

Eight patients with ileal-resection diarrhea who were being treated with cholestyramine took part in a trial comparing the effectiveness of cholestyramine with that of a hydrophilic colloid. Both drugs reduced overall stool frequency and improved consistency, but a larger dose of colloid was required. One patient planned to use the hydrophilic colloid instead of cholestyramine.

Adult↗

Colloid liver SPECT of hepatic alveolar echinococcosis.

Seventy-one-year-old man had a liver mass. He lived in Hokkaido, where there is an epidemic of hydatic disease. Abdominal US image showed an echogenic mass. CT revealed a low density mass with an unclear margin. A 99mTc-Sulfur colloid liver SPECT study was performed to detect the liver mass. The SPECT scan was done after intravenous administration of 5 mCi of 99mTc-sulfur colloid, and it revealed a lack of uptake in the liver mass. The liver SPECT findings were correlated with subsequent CT and US imaging. Echo-guided biopsy showed a PAS-positive cuticle layer of echinococcosis in the necrotic tissue. This is the first report of a case of detection of hepatic alveolar echinococcosis by means of a colloid liver SPECT imaging procedure.

Aged↗