Matches in SemOpenAlex for { <https://semopenalex.org/work/W1495695712> ?p ?o ?g. }
- W1495695712 endingPage "351" @default.
- W1495695712 startingPage "330" @default.
- W1495695712 abstract "Considering that HIV-1 accumulates and replicates actively within lymphoid tissues, any strategy that will decrease viral stores in these tissues might be beneficial to the infected host. Follicular dendritic cells (FDC), B lymphocytes, antigen-presenting cells like macrophages, and activated CD4+ T cells are abundant in lymphoid tissues, and all express substantial levels of the HLA-DR determinant of the major histocompatibility complex class II (MHC-II). Monocyte-derived macrophages, which are also CD4+ and express HLA-DR, are considered to be the most frequent hosts of HIV-1 in tissues of infected individuals. This chapter describes a method for the generation of sterically stabilized immunoliposomes grafted with anti-HLA-DR antibodies that allows efficient delivery of drugs to lymphoid tissues. The method first involves the production of murine HLA-DR (clone Y-17, IgG2b) and human HLA-DR (clone 2.06, IgG1) antibodies from hybridomas in mice and their purification from ascites fluids. This step is followed by the production of Fab′ fragments of antibodies 2.06 and Y-17 that are grafted at the surface of sterically stabilized immunoliposomes instead of the complete IgG to reduce their immunogenicity. The preparation of sterically stabilized liposomes, the composition of which allows an efficient entrapment and retention of several drugs, by the method of thin lipid film hydratation followed by extrusion through polycarbonate membranes is then described. This step is followed by the removal of unencapsulated drug, when present, by low-speed centrifugation of the liposomal preparation through a Sephadex G-50 column. These liposomes contain a fixed amount of poly(ethylene glycol) chain terminated by a maleimide reactive group for the coupling of Fab′ fragments. The procedure for the coupling of Fab′ fragments at the surface of sterically stabilized liposomes and the removal of uncoupled fragments of antibodies is described. In vitro binding studies of sterically stabilized immunoliposomes to cell lines expressing different surface levels of the mouse or human HLA-DR determinant of MHC-II demonstrate that these liposomes are very specific. When compared with conventional liposomes, the subcutaneous administration in the upper back, below the neck, of mice of anti-HLA-DR immunoliposomes resulted in a 2.9 and 1.6 times greater accumulation in the cervical and brachial lymph nodes, respectively. The use of sterically stabilized immunoliposomes increases 2 to 4.6 times the concentration of liposomes in all tissues, with a peak accumulation at 240 h in brachial, inguinal, and popliteal lymph nodes and at 360 h or greater in cervical lymph nodes. A single bolus injection of indinavir given subcutaneously to mice results in no significant drug levels in lymphoid organs. Most of the injected drug accumulates in the liver and is totally cleared within 24 h postadministration. In contrast, sterically stabilized immunoliposomes are very efficient in delivering high concentrations of indinavir to lymphoid tissues for at least 15 days postinjection. The drug accumulation in all tissues leads to a 21- to 126-fold increased accumulation when compared with the free agent. Anti-HLA-DR immunoliposomes containing indinavir are as efficient as the free agent in inhibiting HIV-1 replication in PM1 cells that express high levels of cell surface HLA-DR. Sterically stabilized anti-HLA-DR immunoliposomes mostly accumulate in the cortex in which follicles (B cells and FDCs) are located, and in parafollicular areas in which T cells, interdigitating dendritic cells, and other accessory cells are abundant. The delivery of drugs in this area of the lymph nodes could represent a convenient strategy to inhibit more efficiently HIV-1 replication. Although the method described in this chapter is specific to the coupling of anti-HLA-DR antibodies, any antibody fragment or peptide specific for an antigen present in relatively large quantities at the surface of lymphoid cells, that is anchored to the surface of sterically stabilized liposomes with an appropriate coupling method, can be used to concentrate drugs within target tissues and improve the therapeutic effect of drugs." @default.
- W1495695712 created "2016-06-24" @default.
- W1495695712 creator A5003987523 @default.
- W1495695712 creator A5061371042 @default.
- W1495695712 date "2005-01-01" @default.
- W1495695712 modified "2023-10-18" @default.
- W1495695712 title "Lymphoid Tissue Targeting of Anti-HIV Drugs Using Liposomes" @default.
- W1495695712 cites W1515775405 @default.
- W1495695712 cites W1893364173 @default.
- W1495695712 cites W1964712337 @default.
- W1495695712 cites W1969899610 @default.
- W1495695712 cites W1970622835 @default.
- W1495695712 cites W1977087300 @default.
- W1495695712 cites W1978977138 @default.
- W1495695712 cites W1979779853 @default.
- W1495695712 cites W1988140844 @default.
- W1495695712 cites W1989355526 @default.
- W1495695712 cites W1993342139 @default.
- W1495695712 cites W1994476715 @default.
- W1495695712 cites W2031037912 @default.
- W1495695712 cites W2032943933 @default.
- W1495695712 cites W2041153276 @default.
- W1495695712 cites W2047096261 @default.
- W1495695712 cites W2057442177 @default.
- W1495695712 cites W2069711409 @default.
- W1495695712 cites W2075135942 @default.
- W1495695712 cites W2075171892 @default.
- W1495695712 cites W2076414827 @default.
- W1495695712 cites W2078627102 @default.
- W1495695712 cites W2081550246 @default.
- W1495695712 cites W2082885247 @default.
- W1495695712 cites W2086076672 @default.
- W1495695712 cites W2104106365 @default.
- W1495695712 cites W2107919521 @default.
- W1495695712 cites W2127071167 @default.
- W1495695712 cites W2128256038 @default.
- W1495695712 cites W2139250164 @default.
- W1495695712 cites W2139720961 @default.
- W1495695712 cites W2163715113 @default.
- W1495695712 cites W2173538136 @default.
- W1495695712 cites W2319657764 @default.
- W1495695712 cites W4361867907 @default.
- W1495695712 cites W3152092299 @default.
- W1495695712 doi "https://doi.org/10.1016/s0076-6879(05)91019-7" @default.
- W1495695712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15721390" @default.
- W1495695712 hasPublicationYear "2005" @default.
- W1495695712 type Work @default.
- W1495695712 sameAs 1495695712 @default.
- W1495695712 citedByCount "30" @default.
- W1495695712 countsByYear W14956957122012 @default.
- W1495695712 countsByYear W14956957122013 @default.
- W1495695712 countsByYear W14956957122014 @default.
- W1495695712 countsByYear W14956957122015 @default.
- W1495695712 countsByYear W14956957122018 @default.
- W1495695712 countsByYear W14956957122019 @default.
- W1495695712 countsByYear W14956957122020 @default.
- W1495695712 countsByYear W14956957122022 @default.
- W1495695712 countsByYear W14956957122023 @default.
- W1495695712 crossrefType "book-chapter" @default.
- W1495695712 hasAuthorship W1495695712A5003987523 @default.
- W1495695712 hasAuthorship W1495695712A5061371042 @default.
- W1495695712 hasConcept C147483822 @default.
- W1495695712 hasConcept C153911025 @default.
- W1495695712 hasConcept C159047783 @default.
- W1495695712 hasConcept C159654299 @default.
- W1495695712 hasConcept C185154212 @default.
- W1495695712 hasConcept C185592680 @default.
- W1495695712 hasConcept C203014093 @default.
- W1495695712 hasConcept C2780868878 @default.
- W1495695712 hasConcept C552990157 @default.
- W1495695712 hasConcept C55493867 @default.
- W1495695712 hasConcept C81089528 @default.
- W1495695712 hasConcept C86803240 @default.
- W1495695712 hasConceptScore W1495695712C147483822 @default.
- W1495695712 hasConceptScore W1495695712C153911025 @default.
- W1495695712 hasConceptScore W1495695712C159047783 @default.
- W1495695712 hasConceptScore W1495695712C159654299 @default.
- W1495695712 hasConceptScore W1495695712C185154212 @default.
- W1495695712 hasConceptScore W1495695712C185592680 @default.
- W1495695712 hasConceptScore W1495695712C203014093 @default.
- W1495695712 hasConceptScore W1495695712C2780868878 @default.
- W1495695712 hasConceptScore W1495695712C552990157 @default.
- W1495695712 hasConceptScore W1495695712C55493867 @default.
- W1495695712 hasConceptScore W1495695712C81089528 @default.
- W1495695712 hasConceptScore W1495695712C86803240 @default.
- W1495695712 hasLocation W14956957121 @default.
- W1495695712 hasLocation W14956957122 @default.
- W1495695712 hasOpenAccess W1495695712 @default.
- W1495695712 hasPrimaryLocation W14956957121 @default.
- W1495695712 hasRelatedWork W1980118001 @default.
- W1495695712 hasRelatedWork W2030881267 @default.
- W1495695712 hasRelatedWork W2040191638 @default.
- W1495695712 hasRelatedWork W2050862511 @default.
- W1495695712 hasRelatedWork W2058271852 @default.
- W1495695712 hasRelatedWork W2077863171 @default.
- W1495695712 hasRelatedWork W2113837224 @default.
- W1495695712 hasRelatedWork W2349868750 @default.
- W1495695712 hasRelatedWork W2374954012 @default.