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At least 271 records · Page 15Linked to original sources
PubMed2005

The MammoSite breast brachytherapy device: targeted delivery of breast brachytherapy.

The MammoSite breast brachytherapy device was designed to overcome the logistic difficulties presented by external beam radiation therapy and the technical difficulties of multicatheter-based interstitial brachytherapy. The device consists of a silicone balloon connected to a catheter which contains an inflation channel and a port for passage of a high-dose-rate brachytherapy source. The American Brachytherapy Society and American Society of Breast Surgeons have published partial breast irradiation patient selection guidelines. Initial reports have shown a favorable cosmetic outcome in the majority of patients. The MammoSite applicator has also been associated with minimal side effects. The NSABP B-39/RTOG 0413 trial will randomize patients to either whole breast irradiation or partial-breast irradiation consisting of interstitial brachytherapy, MammoSite brachytherapy, or 3D conformal radiation. This national randomized trial has the potential to provide a definitive answer regarding the benefits of partial-breast irradiation, and therefore lead to more women undergoing breast conserving therapy.

Brachytherapy↗
PubMed2000

Targeted delivery of prostaglandin E1 to hepatocytes using galactosylated liposomes.

Prostaglandin E(1) (PGE(1) ) was incorporated in galactosylated liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)b utyl)formamide (Gal-C4-Chol) intended for hepatocyte-selective delivery. Liposomes composed of distearoylphosphatidylcholine (DSPC)/cholesterol (Chol)/Gal-C4-Chol (60∶35∶5) were prepared and compared with DSPC/Chol (60∶40) liposomes. After intravenous injection of [(3) H]-labeled PGE(1) or cholesteryl hexadecyl ether (CHE) with the liposomal formulation, mice were sacrificed at a series of times, and the radioactivity in tissues was determined. Up to about 80% of [(3) H]CHE in galactosylated liposomes had accumulated in the liver 10 min after intravenous injection and the liver accumulation of the incorporated [(3) H]PGE(1) was significantly higher than that in control liposomes during the entire test period. The pharmacological activity was examined in mice with fulminant hepatitis induced by peritoneal injection of carbon tetrachloride. Intravenous injection of PGE(1) incorporated in DSPC/Chol/Gal-C4-Chol (60∶35∶5) liposomes significantly suppressed the GPT increase, whereas PGE(1) (dissolved in saline) and PGE(1) incorporated in DSPC/Chol (60∶40) liposomes had little effect.

Alanine Transaminase↗
PubMedDate not supplied

[Target delivery of functional genes in gene therapy using carbohydrate containing vectors].

Various aspects of use of specific interactions with a participation of carbohydrate and oligosaccharide ligands to increase an efficiency of gene transfer into eukaryotic cells (including in vivo experiments) are considered in details. Data on addressed gene delivery with applying carbohydrate-containing ligands (such as asialoglycoproteins and galactosides) are discussed in the paper. Results on the usage of glycoside ligands, containing lactose, mannose, glucose residues, for receptor-mediated gene transfer, are analysed. Special attention is paid to application of chitosans for functional gene transfer into eukaryotic cells, which is considered by authors as a case of receptor-mediated gene transfer. It is notice that neo-oligosaccharide vectors, recognizing surface lectins, represent very perspective type of gene delivery systems.

Animals↗
PubMed2003

Preparation, characterization, and preliminary application of fibrinogen-coated olive oil droplets for the targeted delivery of docetaxel to solid malignancies.

Micronized droplets of olive oil loaded with docetaxel (1.0 mg.ml(-1)) and coated with fibrinogen were prepared and then characterized for physicochemical and cytotoxic properties in vitro and anticancer activity in vivo. The droplets remain readily dispersible and relatively stable in size for at least 24 h when stored at 4 degrees C. During storage, the fibrinogen remains bound to the droplets and thrombin coagulable. Nucleoside incorporation assays, growth inhibition assays, and clonogenic assays involving several different tumor cell lines all indicate that the cytotoxicity in vitro of docetaxel applied in olive oil droplets is at least as great as that of docetaxel applied in DMSO. When compared with Taxotere, an equivalent dose of docetaxel administered in fibrinogen-coated oil droplets improved the median survival time of B16F10 melanoma-bearing mice from 21 days to 69 days. Furthermore, whereas none of the Taxotere-treated mice survived longer than 34 days, 33% (three of nine) of the mice treated with docetaxel-loaded, fibrinogen-coated oil droplets were apparently free of disease after 139 days. Preliminary studies indicate fibrinogen adsorbed to docetaxel-loaded oil droplets facilitates the retention of the droplets within the fibrin-rich tumor microenvironment. We propose this new formulation may prove generally useful for the treatment of taxane-sensitive, fibrin-rich tumors.

Animals↗
PubMed1988

Liposomes for targeted delivery of radioiodinated IVdU and 3-CH3-IVdU for non-invasive detection of herpes simplex virus encephalitis in mice.

Liposomal encapsulation of radioiodinated anti-herpes nucleosides was undertaken to reduce metabolic inactivation and increase blood-brain barrier penetration of the nucleosides, and so provide formulations suitable for use in the non-invasive scintigraphic diagnosis of herpes simplex encephalitis (HSE). The nucleosides investigated were [125I]-IVdU and its more lipophilic 3-methyl derivative, and they were encapsulated in phosphatidylcholine:cholesterol:sulfatide liposomes with an efficiency of 4.4% and 1.7% respectively. The encapsulation of IVdU reduced in vitro phosphorolysis (by 31% in serum at 25 degrees C over 3 hr as compared with non-encapsulated IVdU), and markedly increased in vivo stability (fifty-fold greater than that of free drug). In normal mice, higher radioactivity levels were observed in most tissues and there was prolonged, constant blood and brain uptake. Biodistribution of liposomal IVdU in herpes simplex virus (HSV) infected animals was similar, but somewhat lower concentrations were attained. Liposomal encapsulation of [125I]-3-CH3-IVdU produced less dramatic changes in tissue distribution in either healthy or HSV infected mice, as compared with the non-encapsulated drug. Whilst, in HSV infected mice, liposomal encapsulation of both drugs caused increased uptake by spleen, liver and lung, the uptake by brain was still too low for detection by whole-body scintigraphy.

Animals↗
PubMed1996

Targeted delivery of antineoplastic agent to bone: biodistribution studies of technetium-99m-labeled gem-bisphosphonate conjugate of methotrexate.

UNLABELLED: A methotrexate-bisphosphonate conjugate containing a peptide bond has been found to possess over five times greater antineoplastic activity against osteosarcoma in experimental animal models compared with methotrexate alone. METHODS: The conjugate was labeled with 99mTc in the presence of stannous ions to determine biologic distribution, with special reference to osseous tissue. Biodistribution studies were carried out in mice after intravenous administration of the labeled conjugate. Radionuclide imaging of rabbits was also performed. RESULTS: The labeled conjugate behaved like a bone-seeking agent. CONCLUSION: The present study indicates that the concept of treating osteosarcoma or metastatic tumors of bone with this class of agents has a firm basis.

Animals↗
PubMed1997

[Targeting delivery of liposomal adriamycin by intra-lymphatic infusion].

OBJECTIVE: To assess the feasibility of delivering liposomal adriamycin (lipo-ADM) to the regional lymph nodes via intralymphatic infusion in a rabbits model. METHODS: The plasma and tissue ADM levels were measured by high performance liquid chromatography (HPLC) at 0.5 hour, 1 hour, 6 hours, 12 hours, 1 day, 7 days, 14 days, 28 days. RESULTS: The maximum ADM level (Cmax) in the lymph nodes of lipo-ADM was 91.23 micrograms/g, which was 2 times higher than that of the free-ADM group. The area under the ADM concentrations-time curve (AUC) of the regional lymph nodes of lipo-ADM and free-ADM was 138.34 micrograms/day x g-1, 31.86 micrograms/day x g-1 respectively (P < 0.01). The pathological features showed that the lipo-ADM group had more microabscess, necrosis and fibrosis in the lymph nodes than those of the free-ADM group. The histological changes of heart were absent or slight in the lipo-ADM group. CONCLUSIONS: lipo-ADM has a high affinity for lymphatic tissue. Intralymphatic infusion of lipo-ADM may be useful for the treatment of lymphnode metastasis in ovarian cancer.

Animals↗
PubMed2003

Humanized docking system for assembly of targeting drug delivery complexes.

Targeted drug delivery requires 'loading' drugs onto targeting proteins. Traditional technologies for loading drugs rely on chemical conjugation of drugs or drug carriers to targeting proteins. An alternative approach might rely on assembly of targeting complexes using a docking system that includes two components: a 'docking' tag fused to a targeting protein, and a 'payload' module containing an adapter protein for non-covalent binding to the docking tag. We describe here a fully humanized adapter/docking tag system based on non-covalent interaction between two fragments of human pancreatic RNase I. A 15 amino acid long N-terminal fragment of RNase I designed to serve as a docking tag, was fused to the N-terminus of human vascular endothelial growth factor that served as a targeting protein. An 18-125 and an 18-127 amino acid long fragments of RNase I were engineered, expressed and refolded into active conformations to serve as adapter proteins. Interactions between the targeting and adapter proteins were characterized using enzymatic analysis and surface plasmon resonance. Targeting DNA delivery complexes were assembled, characterized by dynamic light scattering, and found to be very effective in receptor-mediated DNA delivery.

Cell Line↗
PubMed2000

Endogenous carriers and ligands in non-immunogenic site-specific drug delivery.

Targeted drug delivery has gained recognition in modern therapeutics and attempts are being made to explore the potentials and possibilities of cell biology related bioevents in the development of specific, programmed and target oriented systems. The components which have been recognized to be tools include receptors and ligands, where the receptors act as molecular targets or portals, and ligands, with receptor specificity and selectivity, are trafficked en route to the target site. Although ligands of exogenous or synthetic origin contribute to the selectivity component of carrier constructs, they may impose immunological manifestations of different magnitudes. The latter may entail a continual quest for bio-compatible, non-immunogenic and target orientated delivery. Endogenous serum, cellular and extracellular bio-ligands interact with the colloidal carrier constructs and influence their bio-fate. However, these endogenous bio-ligands can themselves serve as targeting modules either in their native form or engineered as carrier cargo. Bio-regulatory, nutrient and immune ligands are sensitive, specific and effective site directing handles which add to targeted drug delivery. The present review provides an exhaustive account of the identified bio-ligands, which are not only non-immunogenic in nature but also site-specific. The cell-related bioevents which are instrumental in negotiating the uptake of bio-ligands are discussed. Further, a brief account of ligand-receptor interactions and the set of biological events which ensures ligand-driven trafficking of the ligand-receptor complex to the cellular interior is also presented. Since ligand-receptor interaction is a critical pre-requisite for negotiating cellular uptake of endogenous ligands and anchored carrier cargo, an attempt has been made to identify differential expression of receptors and bio-ligands under normal and etiological conditions. Studies which judiciously utilized bio-ligands or their analogs in negotiating site-specific drug delivery have been reviewed and presented. Targeted delivery of bioactives using endogenous bio-ligands offers enormous options and opportunities through carrier construct engineering and could become a future reality in clinical practice.

Animals↗
PubMedDate not supplied

Polysaccharides for colon targeted drug delivery.

Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients.

Animals↗
PubMed2006

Multiple emulsions: an overview.

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.

Animals↗
PubMedDate not supplied

Synthesis and biological evaluation of paclitaxel-C225 conjugate as a model for targeted drug delivery.

Tumor-targeted drug delivery is an attractive strategy in cancer treatment. We have previously reported a paclitaxel model conjugate using a bombesin receptor-recognizing peptide in which the drug cytotoxicity against H1299 human nonsmall cell lung cancer was enhanced compared to unconjugated taxol. In an effort to expand the development of tumor-recognizing taxanes, paclitaxel (PTX, taxol) was conjugated to the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb) Erbitux (C225) to serve as a model MAb-mediated drug delivery compound. Thus, paclitaxel was derivatized at its 2'-hydroxy function by introduction of a succinate linker, and the carboxyl group of the latter was covalently attached to C225 through amide bond formation. The final product conjugate (PTXC225) was analyzed mass spectrometrically for assessment of the drug-to-antibody ratios. Cytotoxicity screening of the drug-antibody conjugate against A431, UM-SCC-1, and UM-SCC-6 cells indicated an enhancement in cytocidal effect of paclitaxel as compared to those of the free drug, the intact antibody, and a physical mixture of the two (the controls). In A431 cells, the conjugate showed 25.2% +/- 2.2% of apoptosis induction as compared to little or no apoptosis caused by the controls. Biodistribution analysis of the PTXC225 in tumor-implanted nude mice and a tyrosine-kinase assay showed that conjugation of the drug did not interfere with the immunoreactivity of the antibody. The 24-h tumor uptake of C225 and PTXC225 were 11.7% +/- 6.0% and 7.1% +/- 3.6% of the injected dose per gram of tissue (%ID/g), respectively, which were not significantly different. Also, in A431-implanted nude mice, the conjugate and C225 showed tumor growth inhibition effects of 57.2% and 41.2%, respectively, against a saline-treated control, which were not significantly different from each other. This lack of difference in the in vivo antitumor activity of the MAb-delivered drug and free PTX may be due to either a relatively low dose of the antibody-delivered drug (346 microg/kg), or an untimely release of it, or both. The tumor growth inhibition pattern of the conjugate, however, was identical to that of C225, indicating that the attachment of PTX did not affect the antigen-binding and growth inhibitory features of the MAb. These preliminary results demonstrate the potential of tumor-targeted delivery of taxol as a promising strategy in cancer treatment and warrant further work to develop more suitable drug-MAb linkers as well as improved dosage and treatment protocols.

Algorithms↗
PubMed2003

Artificial polymeric cells for targeted drug delivery.

Selectins are optimal biological molecules for targeted delivery of therapeutic agents because of their localized and carefully regulated expression in several human diseases, and their highly specific interactions with their counter receptors. In this study, we describe a targeted delivery system that can potentially deliver anti-inflammatory drug to sites of chronic inflammation using Poly(lactic-co-glycolic acid) (PLGA) and selectin-ligand chemistry. Biotinylated-sialyl Lewis(x) (sLe(x)), a carbohydrate that serves as a ligand to selectins, was attached to the surface of avidin-linked PLGA microspheres. These carbohydrate-coated microspheres mimic the adhesive behavior of leukocytes on selectins in flow chambers, displaying slow rolling under flow. The rolling velocity of these artificial leukocytes is similar to that displayed by leukocytes rolling on P- or E-selectin coated surfaces. We can tune rolling velocity, and hence residence time of capsules on surfaces, by changing the density of sialyl Lewis(x) on the microsphere surfaces. Therefore, we have made a targeted drug delivery vehicle that mimics the adhesive properties of leukocytes and is biodegradable.

Drug Delivery Systems↗