Formulation, characterization, and in vitro release of glyburide from proliposomal beads

The objective of our study was to formulate and evaluate proliposomes in the form of enteric-coated beads using glyburide as a model drug. The beads were enteric coated with Eudragit L-100 by a fluidized bed coating process using triethyl citrate as plasticizer. Content uniformity of glyburide was estimated using HPLC analysis of beads dissolved in methanol. These proliposomal beads formed liposomes on disintegration in phosphate buffered saline (pH 7.4), which was confirmed by transmission electron microscopy. The dissolution study of enteric-coated beads exhibited enhanced dissolution compared with pure drug and a marketed product. Liposomes can be successfully prepared for oral administration in the form of enteric-coated beads that may offer a stable system to produce liposomes for oral administration.     

Amygdalospinal projections in the cat

Spinal cord injections of rhodamine-labeled fluorescent latex microspheres in the cat resulted in retrograde labeling of a dense, well-defined group of neurons within the central nucleus of the amygdala and a modest number of neurons in the medial nucleus. Amygdalospinal neurons were found to be large cells of variable shape and orientation that were distributed bilaterally with an ipsilateral predominence.     

Impact of persistent and cleared preformed HLA DSA on kidney transplant outcomes

Preformed HLA donor-specific antibodies (DSA) only detected with Luminex have been associated with increased risk of antibody-mediated rejection (ABMR) and graft failure after kidney transplantation (KT). Their evolution after KT may modify this risk. We analyzed postransplant evolution of preformed DSA identified retrospectively and their impact on outcomes of 370 KT performed 2006–2014. Antibodies were monitored prospectively at 1-3-5?years after KT and if any dysfunction. Early acute ABMR was more frequent among patients with preformed DSA class-I or I?+?II than isolated class-II (29.4% vs 4.5%, p?=?0.02). One year post-KT, 20 of 34 patients with functioning KT had persistent DSA. Preformed DSA class-II persisted more frequently than class-I/I?+?II (66.7% vs 33.3%; p?=?0.031). The only risk factor independently associated with persistence was pretransplant MFI. Patients with de novo DSA had the highest risk of ABMR (HR 22.2 [CI 6.1–81.2]). Although recipients with persisting preformed DSA had significantly increased ABMR risk (HR 14.7 [CI 6.5–33.0]), those with cleared preformed DSA also had a higher risk than those without DSA (HR 7.01 [CI 2.2–21.8]).Preformed DSA are a very important risk factor for ABMR and graft loss. Patients who clear preformed DSA still show an increased risk of ABMR and graft loss after KT.     

Release characteristics of chitosan treated alginate beads: II. Sustained release of a low molecular drug from chitosan treated alginate beads

The aim of this paper was to investigate the possible applicability of chitosan treated alginate beads as a controlled release system of small molecular drugs with high solubility. Timolol maleate (mw 432.49) was used as a model drug. The beads were prepared by the ionotropic gelation method and the effect of various factors (alginate, chitosan, drug and calcium chloride concentrations, the volume of external and internal phases and drying methods) on bead properties were also investigated. Spherical beads with 0.78-1.16mm diameter range and 10.8-66.5% encapsulation efficiencies were produced. Higher encapsulation efficiencies and retarded drug release were obtained with chitosan treated alginatebeads. Amongthedifferentfactors investigatedsuchas alginate, drug, chitosan and CaCl₂ concentrations, the volumes of the external and internal phases affected bead properties. The drying technique has an importance on the bead properties also. The release data was kinetically evaluated. It appeared that chitosan treated alginate beads may be used for a potential controlled release system of small molecular drugs with high solubility, instead of alginate beads.     

Controlled Release of Ferric-Magnesium Ions From Chitosan/Polyethylene Vinyl Acetate Comatrix for Preventing Pericardial Calcification

Ferric and magnesium ions were embedded in chitosan/polyethylene vinyl acetate comatrix to develop a prolonged release form. The in vitro release profiles of these ions from the comatrix system were monitored in Tris-HCl buffer, pH 7.4, using an ultraviolet (UV) spectrophotometer. The amount of Fe3+ and Mg2+ ions released was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with glutaraldehyde cross-linking of chitosan beads and subsequent styrene butadiene (SBR) coatings on the comatrix. Prostaglandin E was immobilized on this matrix via free1 radical mechanisms, using N plasma to improve their biocompat2 ibility. From scanning electron microscopy studies it appears that the Fe3+/Mg2+ ions diffuse out slowly to the dissolution medium through the micropores of the comatrix. The released Fe3+/Mg2+ ions from the comatrix system had substantially inhibited the pericardial tissue associated calcification, in an in vitro model system. The result proposes the possibility of delivering drug combinations having synergestic effects for therapeutic applications.     

Bovine Serum Albumin–Loaded Pectinate Beads as Colonic Peptide Delivery System: Preparation and In Vitro Characterization

Objective of this study was to prepare a drug delivery system for therapeutic peptides that are degraded in the upper part of the gastrointestinal tract due to degradation activity of the enzymes. Delivering peptide to the colon in which enzymatic activity is low is next hope for absorption of these agents. Pectin, a naturally occurring water soluble polysaccharide, as a matrix for peptide delivery was studied. Degradation of pectin by the colonic enzymes makes it suitable for colon-specific delivery of drugs. Bovine serum albumin (BSA) was used as a model peptide. Calcium pectinate beads were prepared by extruding BSA-loaded pectin solution to an agitating calcium chloride solution, and gelled spheres were formed instantaneously by an ionotropic gelation reaction. The effect of several factors such as concentration of pectin, concentration of calcium chloride, and total drug loading on the pattern of drug release in the dissolution medium was studied. Prepared beads showed good resistance in the release medium. The entrapment efficiency of the beads was high (between 63% and 99%). Entrapment efficiency of BSA was reversely dependent to the amount of the drug loaded in the beads. The amount of BSA loaded on the beads affects pattern of drug release. The concentration of the pectin showed the highest impact on the rate of drug release. Presence of the pectiolytic enzymes facilitated the drug release from the beads.     

Comparison of pharmacokinetics and drug release in tissues after transarterial chemoembolization with doxorubicin using diverse lipiodol emulsions and CalliSpheres Beads in rabbit livers

CalliSpheres^® Beads (CB) is the first drug-eluting bead (DEB) product in China. Our aim was to compare the effect on the pharmacokinetics of doxorubicin (DOX) and its local concentration between lipiodol emulsions and CB in the process of TACE in rabbit livers. Twenty-five rabbits were distributed into two groups; Group 1 received lipiodol emulsions with DOX, and Group 2 received CB loaded with DOX (CBDOX). DOX was measured in the peripheral blood at different times after treatment. Livers were sampled at 1 week and 1 month for Group 2 after embolization. DOX concentration and distribution were measured in the liver. The administration of DOX by TACE with CBDOX resulted in peripheral blood DOX concentrations of 39.85?±?13.86?ng/mL at 5?min, with a gradual decrease to 6.89?±?1.62?ng/mL at 24?h, after treatment. Plasma concentration of DOX after chemoembolization with lipiodol was 225.91?±?64.88?ng/mL at 5?min and decreased with time by 24?h to 5.06?±?0.48?ng/mL. In CBDOX group, the drug impregnated an area as far as 200?μm from the bead edge. The tissue concentration of doxorubicin (tissC_DOX) ranged from 40.27?μg/mL to 245.70?μg/mL at 1 week and from 5.64?μg/mL to 28.09?μg/mL at 1 month. Plasma concentrations of DOX resulting from CBDOX embolization were significantly lower than that for cTACE. CB could deliver relatively high concentrations of DOX to an area as far as 200?μm from the bead edge for at least 1 month.     

Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles

The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits.

SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum.

Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium–carboxylate bonds compared to the coordinate character of their zinc–carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.     

Novel use of Eudragit NE 30D/Eudragit L 30D-55 blends as functional coating materials in time-delayed drug release applications

The objectives of this study were to evaluate the mechanical and thermal properties of films prepared from Eudragit^® NE 30D/Eudragit^® L 30D-55 blends and to examine the dissolution behavior of beads coated with the polymer blends up to 120% weight gain. Eudragit^® NE 30D and L 30D-55 dispersions were blended at 50:50, 67:33, 75:25, and 80:20 ratios. Cast films were evaluated by texture analysis and differential scanning calorimetry. Increasing Eudragit^® NE 30D concentration increased miscibility, softness, and decreased stiffness of the films. At 80:20 ratio, the polymer blend was completely miscible whereby Eudragit^® L 30D-55 was molecularly distributed in the mixture. This was confirmed by SEM analysis. The surface morphology of films and beads was evaluated before and after dissolution by scanning electron microscopy. SEM analysis demonstrated that the size of the pores formed after the dissolution of Eudragit^® L 30D-55 at pH 6.8 was dependent on the miscibility of the Eudragit^® blend. The implications of this effect were apparent in dissolution studies. For the 75:25 and 80:20 blends, a linear increase in lag time up to 7 h was observed with an increase in coat weight gain from 15 to 120%. At 60% weight gain, the 80:20 blend delayed drug release by approximately 7 h whereas the less miscible 75:25 blend delayed drug release by only 3.5 h. A lag time could therefore be controlled by manipulating both the theoretical weight gain of the beads and the concentration of Eudragit^® NE 30D in the blend.     

Insights on novel particulate self-assembled drug delivery beads based on partial inclusion complexes between triglycerides and cyclodextrins

Most of the newly designed drug molecules are lipophilic in nature and often encounter erratic absorption and low bioavailability after oral administration. Finding ways to enhance the absorption and bioavailability of these lipophilic drugs is one of the major challenges that face pharmaceutical industry nowadays. In view of that, the purpose of this review is to shed some light on a novel particulate self-assembling system named “beads” than can act as a safe carrier for delivering lipophilic drugs. The beads are prepared simply by mixing oils with cyclodextrin (CD) aqueous solution in mild conditions. A unique interaction between oil components and CD molecules occurs to form in situ surface-active complexes which are prerequisites for beads formation. This review mainly focuses on the fundamentals of beads preparation through reviewing present, yet scarce, literature. The key methods used for beads characterization are discussed in details. Also, the potential mechanisms by which beads increase the bioavailability of lipophilic drugs are illustrated. Finally, the related research areas that needs to be addressed in future for optimizing this promising delivery system are briefly outlined.