A Novel Approach for the Increased Delivery of Pharmaceutical Agents to Peritoneum and Associated Lymph Nodes

Phillips, William T.; Medina, Luis Alberto; Klipper, Robert; Goins, Beth

doi:10.1124/jpet.102.037119

Cited by 28 publications

(28 citation statements)

References 36 publications

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“…Also the large size of the aggregates may slow down the clearance from the peritoneal cavity or impair the uptake by phagocytic cells. It was shown before that liposomes (average size 130 nm) greatly decreased the clearance of encapsulated drugs out of the peritoneal cavity as compared to the free drug (27). The same authors also showed that the clearance was even more retarded when the liposomes were aggregated via avidin/biotin.…”

Section: Discussionmentioning

confidence: 62%

Structural Characterization and Immunogenicity in Wild-Type and Immune Tolerant Mice of Degraded Recombinant Human Interferon Alpha2b

et al. 2005

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Chapter 6 96 AbstractPurpose. To study the influence of protein structure on the immunogenicity in wildtype and immune tolerant mice of well-characterized degradation products of recombinant human interferon alpha2b (rhIFNα2b).Methods. RhIFNα2b was degraded by metal catalyzed oxidation (M), crosslinking with glutaraldehyde (G), oxidation with hydrogen peroxide (H) and incubation in a boiling water bath (B). The products were characterized with UV absorption, circular dichroism and fluorescence spectroscopy, gel permeation chromatography, reversed-phase HPLC, SDS-PAGE, Western blotting and mass spectrometry. The immunogenicity of the products was evaluated in wildtype mice and in transgenic mice immune tolerant for hIFNα2. Serum antibodies were detected by ELISA or surface plasmon resonance.Results. M-rhIFNα2b contained covalently aggregated rhIFNα2b with three methionines partly oxidized to methionine sulfoxides. G-rhIFNα2b contained covalent aggregates and did not show changes in secondary structure. H-rhIFNα2b was only chemically changed with four partly oxidized methionines. B-rhIFNα2b was largely unfolded and heavily aggregated. Native (N) rhIFNα2b was immunogenic in the wildtype mice but not in the transgenic mice, showing that the latter were immune tolerant for rhIFNα2b. The antirhIFNα2b antibody levels in the wildtype mice depended on the degradation product: M-rhIFNα2b > H-rhIFNα2b ~ N-rhIFNα2b >> B-rhIFNα2b; G-rhIFNα2b did not induce anti-rhIFNα2b antibodies. In the transgenic mice, only M-rhIFNα2b could break the immune tolerance.Conclusions. RhIFNα2b immunogenicity is related to its structural integrity. Moreover, the immunogenicity of aggregated rhIFNα2b depends on the structure and orientation of the constituent protein molecules and/or on the aggregate size. Structural characterization and immunogenicity of rhIFNα2b97

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Section: Discussionmentioning

confidence: 62%

Structural Characterization and Immunogenicity in Wild-Type and Immune Tolerant Mice of Degraded Recombinant Human Interferon Alpha2b

et al. 2005

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“…An eightfold increase in vesicle retention in the popliteal nodes and iliac nodes was noted, and the vesicle aggregates formed could selectively deliver 99m Tc and patent blue violet dye to sentinel lymph nodes. Furthermore, varying the injection site allowed the vesicle aggregates to be targeted to the abdominal and mediastinal lymph nodes (11,12). As expected, labelling avidin with 111 In revealed co-localisation of the avidin and biotin-vesicles within the mediastinal lymph nodes after intrapleural or intraperitoneal injection.…”

Section: (A) Vesicle Cross-linking By Polymers and Proteinsmentioning

confidence: 63%

Creating Functional Vesicle Assemblies from Vesicles and Nanoparticles

2009

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Vesicles (liposomes) have been shown to be excellent vehicles for drug delivery, yet assemblies of vesicles (vesicle aggregates) have been used infrequently in this context. However vesicle assemblies have useful properties not available to individual vesicles; their size can cause localisation in specific tissues and they can incorporate more functionality than is possible with individual vesicles. This article reviews progress on controlling the properties of vesicle assemblies in vitro, applications of vesicle assemblies in vivo, and our recent creation of magnetic nanoparticle-vesicle assemblies. The latter assemblies contain vesicles crosslinked by coated Fe3O4 nanoparticles and this inclusion of magnetic functionality makes them magnetically responsive, potentially allowing magnetically-induced contents release. This article describes further studies on the in vitro formation of these magnetic nanoparticle-vesicle assemblies, including the effect of changing magnetic nanoparticle concentration, pH, adhesive lipid structure and bilayer composition. These investigations have led to the development of thermally-sensitive magnetic nanoparticle-vesicle assemblies that release encapsulated methotrexate on warming.

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“…For this purpose, blue dye was combined with biotin/avidin-liposome labeled with 99m Tc for localizing the sentinel lymph node as well as scintigraphic imaging and quantification of liposome distribution. Rats received intra-peritoneal injections of 99m Tc-HMPAO-bluebiotin-liposome at a dose of 32.7 mg of phospholipid per kilogram and 43 MBq of 99m Tc, after 30 min, followed by intra-peritoneal administration of 5 mg avidin [42]. Higher accumulation of 99m Tc-HMPAO-blue-biotin-liposome in the abdominal nodes and mediastinal nodes and lower spleen level were observed in the experimental group compared to that of the control group.…”

Section: Avidin/biotin-liposomementioning

confidence: 75%

“…Previous studies have reported the high lymph nodal retention of avidin/biotin-liposome through injection of two components (avidin and liposome) at the same injection site [42,43]. This could cause some aggregation in the pleural space and decrease the lymphatic uptake and lymph nodal retention.…”

Section: Avidin/biotin-liposomementioning

confidence: 98%

Molecular Targeting of Liposomal Nano-Particles to Lymphatic System

Nguyen¹,

Hsieh

2011

CCDT

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Conventional liposomal drug delivery has been associated with obvious limitations, such as a rapid absorption by the recticulo-endothelial system in the liver and spleen, a short circulation time and a low therapeutic efficacy. Various modifications of liposomal drugs have been developed to prolong the duration of actions of the drugs at target sites, reduce its adverse effects and increase therapeutic index of drugs such as polymeric conjugation and polymeric fixation on the surface of a liposome. The lymphatic system is an important highway to spread the metastasis of most human cancers including breast, colon, and lung, ovarian and prostate. To eradicate those metastatic cancer cells from the lymphatic system, several efforts have been made to develop new and efficient lymphatic targeting drug delivery systems in order to achieve a high initial lymphatic uptake and lymph node localization. Recently, molecule targeting of liposome to lymphatic system may enhance therapeutic efficacy by improving the initial lymphatic uptake and the lymph nodal retention of liposomes such as the ligand-receptor and antibodies binding on the surface of liposome. This article aims to review the emerging liposomal drug, which is targeting the lymphatic system. The significant factors associated with targeting liposomal drugs will also be discussed in more detail in this review.

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A Novel Approach for the Increased Delivery of Pharmaceutical Agents to Peritoneum and Associated Lymph Nodes

Cited by 28 publications

References 36 publications

Structural Characterization and Immunogenicity in Wild-Type and Immune Tolerant Mice of Degraded Recombinant Human Interferon Alpha2b

Structural Characterization and Immunogenicity in Wild-Type and Immune Tolerant Mice of Degraded Recombinant Human Interferon Alpha2b

Creating Functional Vesicle Assemblies from Vesicles and Nanoparticles

Molecular Targeting of Liposomal Nano-Particles to Lymphatic System

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