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Results for “Targeted delivery”

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PubMed2004

Genetic fusions with viral chemokines target delivery of nonimmunogenic antigen to trigger antitumor immunity independent of chemotaxis.

The ideal vaccine carrier should be able to target antigen delivery and possibly recruit antigen-presenting cells (APC) and deliver an activation signal to promote adaptive immune responses. Ligands for chemokine receptors expressed on APC may be attractive candidates, as they can both target and attract APC. To investigate the requirement for APC recruitment, we used a pair of viral chemokines, agonist herpes simplex virus 8-derived macrophage inflammatory protein-I (vMIP-I) and antagonist MC148, which induce and suppress chemotaxis, respectively. Chemokine-antigen fusions efficiently delivered a model nonimmunogenic tumor antigen to APC for processing and presentation to antigen-specific T cells in vitro. Physical linkage of chemokine and antigen and specific binding of chemokine receptor by the fusion protein were required. Mice immunized with vMIP-I or MC148 fusion DNA vaccines elicited protection against tumor challenge. Therefore, vaccine efficacy depends primarily on the ability of the carrier to target antigen delivery to APC for subsequent processing and presentation, and chemotaxis directly induced by the chemokine moiety in the fusion may not be necessary.

Animals↗

PubMed1996

Synthesis and targeted delivery of an azidothymidine homodinucleotide conferring protection to macrophages against retroviral infection.

The infectivity and replication of human (HIV-1), feline (FIV), and murine (LP-BM5) immunodeficiency viruses are all inhibited by several nucleoside analogues after intracellular conversion to their triphosphorylated derivatives. At the cellular level, the main problems in the use of these drugs concern their limited phosphorylation in some cells (e.g., macrophages) and the cytotoxic side effects of nucleoside analogue triphosphates. To overcome these limitations a new nucleoside analogue homodinucleotide, di(thymidine-3'-azido-2',3'-dideoxy-D-riboside)-5'-5'-p1-p2-pyrophosphat e (AZTp2AZT), was designed and synthesized. AZTp2AZT was a poor in vitro inhibitor of HIV reverse transcriptase, although it showed antiviral and cytotoxic activities comparable to those of the parent AZT when added to cultures of a HTLV-1 transformed cell line. AZTp2AZT encapsulated into erythrocytes was remarkably stable. Induction of erythrocyte-membrane protein clusterization and subsequent phagocytosis of AZTp2AZT-loaded cells allowed the targeted delivery of this impermeant drug to macrophages where its metabolic activation occurs. The addition of AZTp2AZT-loaded erythrocytes to human, feline, and murine macrophages afforded almost complete in vitro protection of these cells from infection by HIVBa-L, FIV, and LP-BM5, respectively. Therefore, AZTp2AZT, unlike the membrane-diffusing azidothymidine, acts as a very efficient antiretroviral prodrug following selective targeting to macrophages by means of loaded erythrocytes.

Animals↗

PubMed2006

Inhibition of tumour metastasis by targeted delivery of antioxidant enzymes.

Metastasis is one of the most harmful aspects of malignant neoplasm. Interaction of tumour cells with normal cells such as tissue macrophages may generate reactive oxygen species, which would affect various aspects of tumour metastasis. Reactive oxygen species cause damage to both tumour and normal cells and some of them, especially hydrogen peroxide, can also act as intracellular second messengers at sublethal concentrations to increase the transcription of various genes, which can then accelerate the proliferation of tumour cells in metastatic colonies. Therefore, eliminating hydrogen peroxide is one approach to inhibiting tumour metastasis. In this article, the roles of reactive oxygen species in tumour metastasis are reviewed, and the strategies to inhibit tumour metastasis by the targeted delivery of catalase, an enzyme that detoxifies hydrogen peroxide, are discussed.

Animals↗

PubMed2002

[Opinion of colon-targeting delivery about rhubarb extract as a purgative].

OBJECTIVE: To elucidate that rhubarb extract as a purgative should be delivered to colon from a pharmaceutical point of view. METHOD: Effects of anthranoids and free anthraquinones as purgatives on the colon motility and transit time, the absorption in vivo, and the loss in the processes of extraction, concentration and dryness were reviewed, based on the recent 60 years pharmacological, pharmaceutical and clinical experimental studies at home and abroad. RESULT AND CONCLUSION: Free anthraquinones in rhubarb extract should be regarded as purgative principles. Close attention should be paid to the loss of free anthraquinones not only in the processes of extraction, concentration and dryness, but also in the process of transit in the upper gastrointestinal tract. Colon-targeting delivery of rhubarb extract, as a purgative, may prevent absorption of free anthraquinones in the upper gastrointestinal tract, thus improving clinical effects and lowering dosage.

Animals↗

PubMed1998

A cell adhesion peptide from foot-and-mouth disease virus can direct cell targeted delivery of a functional enzyme.

The G-H loop of foot-and-mouth disease virus is a disordered protrusion of the VP1 protein exposed on the virion surface. This short stretch includes an arginine-glycine-aspartic acid tripeptide, a recognized integrin-binding motif, which is responsible for cell attachment and infection. Eight copies of a peptide reproducing the amino acid sequence of this FMDV ligand have been displayed in solvent-exposed regions on an enzymatically active recombinant beta-galactosidase. This viral peptide segment enables the chimeric enzyme to bind mammalian cell lines with different efficiencies, probably depending on the number of suitable cell receptors present on each of them. Moreover, it also promotes the internalization of the attached enzyme, which is transiently active inside the cells. These results suggest further exploration of the potential use of short adhesion peptides of viral origin as cell attachment tags to direct the targeted delivery of both genes and enzymes, instead of whole, infectious viruses.

Amino Acid Sequence↗

PubMed2006

Antibody-conjugated soybean oil-filled calcium phosphate nanoshells for targetted delivery of hydrophobic molecules.

Hollow calcium phosphate nanoparticles capable of encapsulating poorly water-soluble molecules were produced by self-assembly. Previously reported were solid calcium phosphate nanoparticles and water-filled calcium phosphate nanocapsules suited for encapsulating mostly hydrophilic, but not hydrophobic compounds. Here, calcium phosphate was deposited around 100 nm diameter, 1,2-dioleoyl-sn-glycero-3-phosphate stabilized soybean oil nanoemulsions using either calcium chloride or NaOH titrations to achieve shell thickness between 20-70 nm. The surface was functionalized with carboxylic acid via the addition of carboxyethylphosphonic acid to attach Molecular Probes AB-594C antibody using sulpho-n-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with an efficiency of approximately 70%, while retaining near complete antibody function. Hydrophobic pyrene was encapsulated with an efficiency of 95%, at concentrations much higher than its water solubility limit, and exhibited spectral features characteristic of a hydrophobic environment. These materials can be used in the targeted delivery of many useful, yet poorly water-soluble pharmaceutical and nutraceutical compounds.

Antibodies↗

PubMed2004

Inhibition of experimental hepatic metastasis by targeted delivery of catalase in mice.

Bovine liver catalase derivatives possessing diverse tissue distribution properties were synthesized, and their effects on hepatic metastasis of colon carcinoma cells were examined in mice. An intraportal injection of 1 x 10(5) colon 26 cells resulted in the formation of more than 50 metastatic colonies on the surface of the liver at 14 days after injection. An intravenous injection of catalase (CAT; 35000 units/kg of body weight) significantly (P < 0.001) reduced the number of the colonies in the liver. Galactosylated (Gal-), mannosylated (Man-) and succinylated (Suc-) CAT were also tested in the same system. Of these derivatives, Gal-CAT showed the greatest inhibitory effect on hepatic metastasis, and the number of colonies was significantly (P < 0.001) smaller than following treatment with catalase. High activities of matrix metalloproteinases (MMPs), especially MMP-9, were detected in the liver of mice bearing metastatic tumor tissues, which was significantly (P < 0.05) reduced by Gal-CAT. These results, combined with our previous finding that Gal-CAT can be efficiently delivered to hepatocytes, indicate that the targeted delivery of catalase to the liver by galactosylation is a promising approach to suppress hepatic metastasis. Decreased MMP activity by catalase delivery seems to be involved in its anti-metastatic effect.

Animals↗

PubMed2006

Reversible vagal blockade in conscious rats using a targeted delivery device.

Reversible methods of nerve blockade greatly aid neurophysiological and behavioral studies. We have developed an implantable device for the local delivery of anesthetics to the area surrounding the vagal nerve in rats. The device consists of a thick silicone tube for insulating the nerves from the surrounding tissue, and a thin silicone tube for the infusion of anesthetics into the insulating tube. The in vivo performance of the device was tested electrophysiologically, and cardiovascular responses to vagal stimulation were measured in conscious animals. Nerve conductivity was completely blocked by injection of a small amount (<20 microl) of 1% lidocaine, with conductivity subsequently recovering gradually after 10-40 min. Electrical stimulation of the right vagus nerve in conscious rats increased arterial pressure while decreasing heart rate. The local blockade of afferent fibers abolished the arterial pressure response but preserved the bradycardic response to vagal nerve stimulation. The targeted delivery device was useful for reversible vagal blockade in conscious rats.

Anesthetics, Local↗

PubMed2005

Studies on the targeted delivery of the antifibrogenic compound mycophenolic acid to the hepatic stellate cell.

BACKGROUND/AIMS: Hepatic stellate cell (HSC) activation and proliferation are key events in the pathology of liver fibrosis. Inhibiting these parameters, therefore, is a relevant option to treat liver fibrosis pharmacologically. The immunosuppressive drug mycophenolic acid (MPA) has been shown to inhibit proliferation and activation of various types of fibroblasts. In an effort to circumvent the immunosuppression and at the same time enhance this antifibrotic effect, we coupled MPA to the HSC-selective drug carrier mannose-6-phosphate modified human serum albumin and evaluated this conjugate for its specificity and antifibrotic activity. METHODS/RESULTS: We found that MPA inhibited proliferation of HSC in vitro. The drug coupled to the drug carrier bound specifically to HSC and reduced HSC proliferation in vitro. In vivo studies demonstrated that our conjugate accumulated selectively in the liver with significant uptake in HSC apart from Kupffer and endothelial cells, whereas primary and secondary lymphoid tissues were avoided. Treatment of bile duct-ligated rats with this conjugate reduced hepatic inflammation and hepatic alpha-beta-Crystallin mRNA expression, a marker for HSC activation. CONCLUSIONS: This study shows that targeted delivery of MPA to HSC results in a decrease in HSC activation, making it the first drug that is successfully delivered to this cell type.

Animals↗

PubMed2006

Construction and evaluation of novel fusion proteins for targeted delivery of micro particles to cellulose surfaces.

The use of IgG antibodies and fragments has been limited to specific sectors of the biotechnology industry due to the high cost of producing large batches of product necessary for alternative applications. A novel class of Camelid antibodies, known as V(HH) offer a more economical opportunity to meet a wider application in industry. In this study, we report the evaluation of four llama V(HH)-cellulose binding domain fusion proteins displaying varying formats of V(HH) and CBD domains. Proteins were characterized in a targeted particle delivery system as a method of delivering agents such as perfume to laundry in the wash cycle. Fusion proteins were shown to be stable at high pH and in the presence of a detergent base. They were also shown to bind effectively to both the designated antigen, the azo-dye reactive-red 6 (either conjugated to BSA or attached to coacervate microparticles), and cellulose. Binding strength differences were observed between the different fusion protein formats using surface plasmon resonance. The effect of key laundry ingredients was also studied. Combining the fusion proteins and particles into a delivery and deposition study generated clear microscopy evidence for bifunctionality. Confirmation of this was validated by GC-MS analysis of retained fragrance. This research, reporting the construction and characterization of a variety of fusion proteins, illustrates that the single multidomain fusion protein route offers a new technology for successful targeted delivery of encapsulated benefit agents. Furthermore, the potential to modify or select for proteins to recognize a wide range of surfaces is also possible.

Amino Acid Sequence↗

PubMedDate not supplied

Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model.

HYPOTHESIS: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. METHODS: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. RESULTS: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63+/-1.99 vs. 4.77+/-.1.71 mm2, respectively, P<.05). CONCLUSION: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

Animals↗

PubMed2002

Tumor-targeted delivery of polyethylene glycol-conjugated D-amino acid oxidase for antitumor therapy via enzymatic generation of hydrogen peroxide.

Hydrogen peroxide (H(2)O(2)) is a strong oxidant that induces apoptosis of tumor cells in vitro. Here, we investigated the antitumor activity of an H(2)O(2)-generating enzyme, D-amino acid oxidase (DAO), and its conjugate with polyethylene glycol (PEG; PEG-DAO). Compared with DAO, PEG-DAO showed improved pharmacokinetic parameters in mice after i.v. injection. PEG-DAO administered i.v. accumulated selectively in tumor tissue with insignificant accumulation in normal organs and tissues. To generate cytotoxic H(2)O(2) at the tumor site, PEG-DAO was first administrated i.v. to tumor-bearing mice. After an adequate lag time, the substrate of DAO, D-proline, was injected i.p. This treatment resulted in significant suppression of tumor growth compared with tumor growth in control animals (not given treatment; P < 0.001). Similar treatment with native DAO showed no effect under the same conditions. Oxidative metabolites were significantly increased in solid tumors by administration of PEG-DAO followed by D-proline (P < 0.002, compared with the group receiving no treatment), as evidenced by thiobarbituric acid-reactive substance assay. This treatment did not affect results from the metabolites in the liver and kidney. These findings suggest that tumor-targeted delivery of DAO is accomplished by using pegylated enzyme and thereby taking advantage of the enhanced permeability and retention effect in solid tumor. PEG-DAO thus delivered together with D-proline produces remarkable antitumor activity via extensive generation of H(2)O(2).

Animals↗

PubMed2006

Sustained and targeted delivery of an anti-HIV agent using elastic liposomal formulation: mechanism of action.

The present study is aimed at evaluating the transdermal route as an alternative to the oral route for improving the systemic bioavailability and sustaining the constant therapeutic plasma level of Zidovudine (AZT). Elastic liposomal formulations of AZT were prepared and characterized. The effect of different formulation variables on transdermal delivery of AZT from elastic liposomes was studied. To investigate the mechanism of skin permeation of elastic liposomes, Transmission Electron Microscopic (TEM) study was carried out. The optimized elastic liposomal formulation showed transdermal flux of 98.8+/-5.8 microg/cm2/hr across rat skin as compared to 5.72+/-0.3 microg/cm2/hr for free drug. Vesicle-skin interaction study showed that elastic vesicles influenced the ultra structure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular spaces of the stratum corneum. These stacks disrupted the organization of skin bilayers leading to increased skin permeability, whereas no changes were observed in the underlying viable epidermis and dermis. Improved pharmacokinetic profile was observed when AZT was entrapped in elastic liposomes. The AUC0-24h for elastic liposomal formulation was found to be (12.63+/-1.2 microg h/mL), nearly twelve fold higher than the control (0.83+/-0.2 microg h/mL). Furthermore, the administration of elastic liposome encapsulated AZT resulted in substantially higher accumulation of AZT in target RES organs that play a key role in the pathogenesis of AIDS by providing long-term reservoir for the virus. The results of the present study demonstrated that elastic liposomes increased the transdermal flux, prolonged the release, improved the site specificity of AZT and represented an attractive strategy for sustained and targeted delivery of AZT.

Administration, Cutaneous↗

PubMed1997

Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal administration.

Administration, Intranasal↗

PubMed2006

Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin.

PURPOSE: We sought to demonstrate that a single systemic administration of L19mTNFalpha (a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and tumor necrosis factor alpha, TNFalpha) in combination with melphalan induced complete and long-lasting tumor eradication in tumor-bearing mice and triggered the generation of a specific T cell-based immune response that protects the animals from a second tumor challenge, as well as from challenges with syngeneic tumor cells of different histologic origin. EXPERIMENTAL DESIGN AND RESULTS: Treatment with L19mTNFalpha, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also rejected challenges with syngeneic tumor cells of different histologic origin. In adoptive immunity transfer experiments, the splenocytes from tumor-cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. CONCLUSIONS: The results show that the selective targeting of mTNFalpha to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFalpha to the tumor vasculature.

Animals↗

PubMed1996

Pharmacokinetic study of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate after targeted delivery to the lung in mice.

This study describes the pharmacokinetic behaviours of taxol after intravenous administration of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate (namely, Taxol-IPM-PLGA-MS) and taxol saline solution to mice. Taxol-IPM-PLGA-MS were prepared using a solvent evaporation technique. The drug content and trapping efficiency of taxol in the microspheres were 5.09% (w/w) and 98%, respectively; the average diameter of the microspheres was 30.1 microns. Scanning electron microscopy showed that Taxol-IPM-PLGA-MS were spherical with a smooth surface. After administration of the drug saline solution (3 mg taxol/kg), taxol disappeared rapidly from plasma within 4-6 h and distributed extensively in various tissues. The tissue levels and AUCfinite of taxol in the lung were obviously higher than those in plasma but relatively lower than those in kidneys, bile, and liver. The biodistribution of taxol after administration of Taxol-IPM-PLGA-MS (3 mg taxol/kg), on the other hand, was altered significantly from the control (taxol solution) group. No taxol was detected in plasma or bile within 3 weeks, and only very low level of taxol was detected in the kidneys or liver within 48 h. However, taxol concentrations in the lung were increased significantly with the microsphere group; the peak concentration of taxol and AUCfinite in the lung was three times and 500 times higher than those with the taxol solution group, respectively. It was also noticed that the taxol levels in the lung were maintained at relatively high levels (> 10 micrograms/ml) for 3 weeks. Thus, the present study demonstrated the effective targeted delivery of taxol to the lung of mice using Taxol-IPM-PLGA-MS.

Animals↗

PubMed1999

Targeted delivery of anti-angiogenic agent TNP-470 using water-soluble polymer in the treatment of choroidal neovascularization.

PURPOSE: The conjugation of drugs with water-soluble polymers such as poly(vinyl alcohol) (PVA) tends to prolong the half-life of drugs and facilitate the accumulation of drugs in tissues involving neovascularization. The purpose of this study was to evaluate the effect of TNP-470-PVA conjugate on the proliferation of endothelial cells in vitro and on experimental choroidal neovascularization (CNV) in vivo. METHODS: TNP-470 was conjugated in PVA by a dimethylaminopyridine-catalyzed reaction. The effects of TNP-470-PVA and free TNP-470 on the proliferation of human umbilical vein endothelial cells (HUVECs) and bovine retinal pigment epithelial cells (BRPECs) were evaluated by the tetrazolium-based colorimetric assay (XTT assay). Experimental CNV was induced by subretinal injection of gelatin microspheres containing basic fibroblast growth factor, into rabbits. Thirty rabbits were intravenously treated either with TNP-470-PVA (n = 8), free TNP470 (n = 5), free PVA (n = 5), or saline (n = 12) daily for 3 days, 2 weeks after implantation of gelatin microspheres. Fluorescein angiography was performed to detect the area with CNV, and the evaluation was made by computerized measurement of digital images. These eyes were also examined histologically. To observe the accumulation of conjugate, 3 rabbits with CNV received rhodamine B isothiocyanate-binding PVA (RITC-PVA), and the lesion was studied 24 hours later by fluorescein microscopy. RESULTS: The TNP-470-PVA inhibited the growth of HUVECs, similar to that of free TNP-470. The BRPECs were less sensitive to TNP-470-PVA than were the HUVECs. TNP-470-PVA significantly inhibited the progression of CNV in rabbits (P = 0.001). Histologic studies at 4 weeks after treatment demonstrated that the degree of vascular formation and the number of vascular endothelial cells in the subretinal membrane of the eyes treated with TNP-470-PVA were less than those of the control eyes. RITC-PVA remained in the area with CNV 24 hours after administration. CONCLUSIONS: These results suggest that TNP-470-PVA inhibited the proliferation of HUVECs more sensitively than that of BRPECs, and the targeted delivery of TNP-470-PVA may have potential as a treatment modality for CNV.

Animals↗

PubMed1992

[Efficacy of preoperative adjuvant chemotherapy using adriamycin targeting the regional lymph nodes for gastric cancer--lymph node-targeting delivery of adriamycin in rabbits].

Chemotherapy targeting the regional lymph nodes for gastric cancer may be more effective preoperatively than postoperatively since anticancer drugs can be transported to the regional lymph nodes via the lymphatic flow through the stomach. Distribution of Adriamycin (ADR) among the various organs was assessed following its intravenous injection in rabbits. The delivery index of the drug to each organ was assessed by the ratio of the area under the concentration-time curve (AUC) of each organ to the AUC of the regional lymph nodes following the intravenous administration. The delivery index was 0.14 for the stomach, 0.11 for the heart, 0.53 for bone marrow, 0.74 for the spleen, and 0.14 for the liver. These data suggest that preoperative adjuvant chemotherapy by intravenous administration of ADR may be effective in targeting ADR at the regional lymph nodes. Tissue ADR concentrations in the regional lymph nodes were assessed following gastric submucosal administration of ADR in rabbits. The targeting index for the regional lymph nodes was 8.20, measured by the ratio of AUC following a gastric submucosal injection to AUC after the intravenous injection of ADR. This suggests that it may be possible to selectively target chemotherapy to regional lymph nodes by employing a gastric submucosal administration of ADR.

Animals↗