Macrolactones and polyesters from ricinoleic acid.

A systematic study on the synthesis, characterization, and polymerization of ricinoleic acid (RA) lactone is reported. Ricinoleic acid lactones were synthesized by refluxing pure ricinoleic acid in chloroform (10 mg/mL) with dicyclohexylcarbodimide and (dimethylamino)pyridine as catalyst. Purification of RA lactones was performed by silica gel chromatography.

The effect of amphotericin b derivatives on Leishmania and immune functions.

The effects of a water-soluble amphotericin B (AmB)-arabinogalactan (AG) conjugate on several immune functions were investigated. The experiments measured the effects of AmB-AG on (1) release of tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), and interferon-gamma (IFN-gamma) from phagocytic cells and (2) cell-mediated immune responses. AmB-AG increased TNF-alpha release from mouse peritoneal macrophages and human monocytes but had no effect on IFN-gamma and NO release.

Role of polyanhydrides as localized drug carriers.

Many drugs that are administered in an unmodified form by conventional systemic routes fail to reach target organs in an effective concentration, or are not effective over a length of time due to a facile metabolism. Various types of targeting delivery systems and devices have been tried over a long period of time to overcome these problems. Targeted delivery or localized drug delivery offers an advantage of reduced body burden and systemic toxicity of the drugs, especially useful for highly toxic drugs like anticancer agents.

Induction of interleukin-1beta, tumour necrosis factor-alpha and apoptosis in mouse organs by amphotericin B is neutralized by conjugation with arabinogalactan.

Objectives: To investigate the possibilities that: (i) organ toxicity of amphotericin B-deoxycholate (AMB-DOC) is related to induction of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and apoptosis in target organs; and (ii) the reduced toxicity resulting from the conjugation of AMB with water-soluble arabinogalactan (AMB-AG), is related to modulation of these parameters.

Methods: Organ expression of IL-1beta and TNF-alpha was evaluated by enzyme-linked immunosorbent assay (ELISA) in mouse organ biological fluids and in situ by immunohistochemistry. Tissue damage was evaluated histologically, and apoptosis was demonstrated by terminal dUTP nick end-labelling (TUNEL) staining.

Cationic polysaccharides as antiprion agents.

Cationic polysaccharides were synthesized by conjugation of various oligoamines to oxidized polysaccharides by reductive amination and tested for antiprion activity. Polycations of dextran, pullulan and arabinogalactan grafted with oligoamines of 2 to 4 amino groups were investigated for their ability to eliminate PrP(Sc), the protease-resistant isoform of the prion protein, from chronically infected neuroblastoma cells, ScN2a-M. The proteinase K (PK)-resistant PrP elimination depends on both the concentration of the reagent and the duration of exposure.

Normal phase high performance liquid chromatography for determination of paclitaxel incorporated in a lipophilic polymer matrix.

A normal phase (NP) high performance liquid chromatography (HPLC) method was developed for analysis of paclitaxel incorporated in poly(sebacic-co-ricinoleic acid), a lipophilic polymer matrix utilized for preparation of an injectable formulation for the localized delivery of paclitaxel. Thin layer chromatography experiments revealed that separation of paclitaxel from the polymer is dependent on the eluting strength (solvent strength) of the mobile phase. The HPLC system consists of a Purospher STRAR Si analytical HPLC column (5 microm, 250mm x 4mm, Merck), and 1-2.

Novel dextran-spermine conjugates as transfecting agents: comparing water-soluble and micellar polymers.

Recently, a novel cationic polymer, dextran-spermine (D-SPM) was developed for gene delivery. An efficient transfection was obtained using this polycation for a variety of genes and cell lines in serum-free or serum-poor medium. However, transfection using the water-soluble D-SPM-based polyplexes decreased with increasing serum concentration in cell culture in a concentration-dependent manner, reaching 95% inhibition at 50% serum in the cell growth medium.

[A new gel for topical use in treating severe periodontal disease--clinical observations].

Within the framework of the efforts to find non-invasive treatment methods for severe periodontitis, a topical gel was developed by an Israeli research group. The aim of the current study is to present clinical observations and X-ray measurements of alveolar bone changes following an 8 week, self-care periodontal treatment in two groups of patients with severe periodontitis. All 31 patients who participated in the study showed an improvement of the periodontal condition as expressed in all the indexes examined.

Adhesive tablet effective for treating canker sores in humans.

A new mucoadhesive tablet, which releases natural active agents for pain reduction and rapid healing of canker sores, has been prepared and characterized. Adhesive tablets were prepared by compression molding of mixed powders of crosslinked polyacrylic acid and hydroxypropyl cellulose, absorbed with citrus oil and magnesium salt. The rate of tablet erosion and the rates of citrus oil and magnesium release were determined as well as the adhesiveness of the tablet using bovine gingival tissue and an Instron tensiometer.

Hetero-stereocomplexes of D-poly(lactic acid) and the LHRH analogue leuprolide. Application in controlled release.

Reversible hetero-stereoselective complexes were obtained by mixing acetonitrile solutions of enantiomeric D-poly(lactic acid) (d-PLA) and leuprolide, an L-configured nonapeptide LHRH analogue. The complex spontaneously aggregated and precipitated in high yields (95%) from acetonitrile solutions, forming uniform, porous microparticles with a mean unweighed particle size of 1.7 microm.

Distribution of amphotericin B-arabinogalactan conjugate in mouse tissue and its therapeutic efficacy against murine aspergillosis.

The pharmacokinetic characteristics and tissue distribution of a novel water-soluble, nontoxic amphotericin B-arabinogalactan (AMB-AG) conjugate exhibited distinct differences from those of micellar and liposomal amphotericin B formulations. These differences included extended persistence of drug in the body and its accumulation in the lungs; thus, the AMB-AG conjugate was highly effective in treating systemic murine aspergillosis.

Preparation and characterization of n-alkanoic acid self-assembled monolayers adsorbed on 316L stainless steel.

The electrochemical formation and characterization of decanoic, myristic, palmitic, and stearic acid self-assembled monolayers on a native oxide surface of 316L stainless steel have been studied. This work describes a new approach to surface modification of stainless steel in which the self-assembly of n-alkanoic acids is facilitated by applying a potential to the stainless steel in an organic electrolyte solution. While decanoic acid forms a disorganized monolayer as a result of sweeping the potential in an acetonitrile solution containing 0.

Delivery of gentamicin to the rabbit eye by drug-loaded hydrogel iontophoresis.

Purpose: To assess the corneal iontophoretic delivery of gentamicin by drug-loaded hydrogel probe, and to determine the resultant ocular disposition and elimination of the drug from the cornea and anterior chamber.

Methods: Corneal iontophoresis of gentamicin sulfate was studied in healthy white rabbits by using drug-loaded disposable hydroxyethyl methacrylate (HEMA) hydrogel disk probes and a portable mini-ion device designed in the authors' laboratory. The iontophoretic treatment was performed with a current intensity of 1 mA for 60 seconds only.

Protein and peptide parenteral controlled delivery.

Protein and peptide delivery has been a challenge due to their limited stability during preparation of formulation, storage and in vitro and in vivo release. These biopolymers have traditionally been administered via intramuscular or subcutaneous routes. Recent efforts have been made to develop formulations for non-invasive routes of administration, including oral, intranasal, transdermal and transmucosal delivery.

Hydrogel probe for iontophoresis drug delivery to the eye.

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface.

Iontophoresis-gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe.

Purpose: To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel-gentamicin containing probe.

Methods: Eight of 10 groups (groups 3-10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0.

Hydrophobized dextran-spermine conjugate as potential vector for in vitro gene transfection.

Dextran polysaccharide was grafted by reductive-amination with mixtures of spermine and other natural/synthetic oligoamines of two to four amine groups. The transfection efficiencies of the polycations thus obtained were assessed in various cell lines, and found to depend on the spermine contents. Higher spermine ratios of grafted oligoamines resulted in high gene expression, whereas low to negligible expressions were obtained with lower spermine contents.

Cyclosporin nanoparticulate lipospheres for oral administration.

Cyclosporin is a first line immunosuppressive drug used to prevent transplant rejection and to treat autoimmune diseases. It is a hydrophobic cyclic peptide built from nonmammalian amino acids with low oral bioavailability. The aim of this study was to develop an oral delivery system for cyclosporin A (CyA) and investigate the effect of composition and particle size of the CyA lipid nanoparticles (lipospheres) on the oral bioavailability of this drug.

AMD3100 conjugates as components of targeted nonviral gene delivery systems: synthesis and in vitro transfection efficiency of CXCR4-expressing cells.

We describe the synthesis of a series of AMD3100-lipid and AMD3100-polycationic conjugates which were used as components of targeted lipoplexes (in conjunction with (poly)cationic lipids) and polyplexes, respectively, for mediating specific gene transfer into cells expressing CXCR4 which displays a high affinity for AMD3100. Transfection studies were investigated with suspension CXCR4(+) human lymphoma Jurkat cells and with adherent CXCR4(-) human glioblastoma T98G and human lung carcinoma A549 cells lines in order to demonstrate a receptor-mediated endocytosis pathway and to minimize nonspecific transfection pathways. Altogether, our results show that polyplexes formulated with AMD-labeled polymers constitute, under certain conditions, specific gene transfer systems into suspension CXCR4(+) Jurkat cells.

Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel: in vitro release and in vivo toxicity.

Polyesteranhydrides synthesized by the transesterification of ricinoleic acid and sebacic acid followed by anhydride polymerization were examined as potential controlled delivery carrier for paclitaxel. Solid and liquid polymers were used. Polymers containing 30% ricinoleic acid are solid whereas polymers containing 70% ricinoleic acid are liquid at body temperature and semisolid at room temperature.

Conjugation of amino-containing drugs to polysaccharides by tosylation: amphotericin B-arabinogalactan conjugates.

The coupling of amphotericin-B (AmB), a water-insoluble antifungal and antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate derivatives was investigated as a method for the conjugation of amino-containing drugs to polysaccharides. In the first step, AG was reacted with tosyl- or mesyl-chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB was conjugated to AG derivatives in either aqueous or organic media via an amine bond.

Intravenous and regional paclitaxel formulations.

Paclitaxel has been proven to be effective against different types of cancer. A delivery system loaded with paclitaxel at tumor site should provide a high local concentration of the drug detrimental to malignant cells, which prevents the re-growth and metastasis of tumor. In this review, paclitaxel formulations for systemic and for intratumoral administration are discussed.

Dextran-spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection.

Dextran-spermine cationic polysaccharide was prepared by means of reductive amination between oxidized dextran and the natural oligoamine spermine. The formed Schiff-base imine-based conjugate was reduced with borohydride to obtain the stable amine-based conjugate. The transfection efficiency of the synthetic dextran-spermine was assessed in vitro on HEK293 and NIH3T3 cell lines and found to be as high as the DOTAP/Chol 1/1 lipid-based transfection reagent.