Frontiers in Medicinal Chemistry

Volume: 9

Targeted Drugs and Nanomedicine: Present and Future

Author(s): Gudrun C. Thurner, Monika Chabicovsky, Alshaimaa Abdelmoez and Paul Debbage

Pp: 182-233 (52)

DOI: 10.2174/9781681082493116090008

* (Excluding Mailing and Handling)

Abstract

Packaging small-molecule drugs into nanoparticles improves their bioavailability, bio-compatibility and safety profiles. Multifunctional particles carrying large drug payloads for targeted transport, immune evasion and favourable drug release kinetics at the target site, require a certain minimum size usually 30-300 nm diameter, so are nanoparticles. Targeting particles to a disease site can signal the presence of the disease site, block a function there, or deliver a drug to it. Targeted nanocarriers must navigate through blood-tissue barriers, varying in strength between organs and highest in the brain, to reach target cells. They must enter target cells to contact cytoplasmic targets; specific endocytotic and transcytotic transport mechanisms can be used as trojan horses to ferry nanoparticles across cellular barriers. Specific ligands to cell surface receptors, antibodies and antibody fragments, and aptamers can all access such transport mechanisms to ferry nanoparticles to their targets. The pharmacokinetics and pharmacodynamics of the targeted drug-bearing particle depend critically on particle size, chemistry, surface charge and other parameters. Particle types for targeting include liposomes, polymer and protein nanoparticles, dendrimers, carbon-based nanoparticles e.g. fullerenes, and others. Immunotargeting by use of monoclonal antibodies, chimaeric antibodies and humanized antibodies has now reached the stage of clinical application. High-quality targeting groups are emerging: antibody engineering enables generation of human/like antibody (fragments) and facilitates the search for clinically relevant biomarkers; conjugation of nanocarriers to specific ligands and to aptamers enables specific targeting with improved clinical efficacy. Future developments depend on identification of clinically relevant targets and on raising targeting efficiency of the multifunctional nanocarriers. The complexity and expense of translational work with nanoparticles has prompted regulatory agencies and funding organizations to adapt regulatory frameworks and establish programs to facilitate preclinical testing.


Keywords: Antibody fragments, aptamers, clinical trials, immunotargeting, liposomes, nanomedicine, nanoparticles, regulatory issues, targeted drugs, tissue barriers.

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      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 11. app/Models/ContentAccess.php:647
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      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51413955 and j.to_ip >=51413955 )) and ((j.from_date <= 1739847122 and j.to_date >= 1739847122 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8739) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51413955 and j.to_ip >=51413955 )) and ((j.from_date <= 1739847122 and j.to_date >= 1739847122 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8739) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51413955 and j.to_ip >=51413955 )) and ((j.from_date <= 1739847122 and j.to_date >= 1739847122 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8739)
      620μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1925 and `b`.`banner_from_date` <= 1739847122 and `b`.`banner_to_date` >= 1739847122 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1925
      • 3: 1739847122
      • 4: 1739847122
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='e037f12a05fec4862ade479061fd473d'
      260μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    10Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        WxUH0qAH3hdaoesU0afneRRSYIHfxepWJCGylzeW
        uc_cart_id
        e037f12a05fec4862ade479061fd473d
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/8739" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/8739
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 18 Feb 2025 02:52:02 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldUZUFlbFp0ay8yNUlHUHZ1VXJ3eHc9PSIsInZhbHVlIjoiak42Y2hGR2pIcTV1UmtnSDZJZ0FqdTRkWDRlNUhiYVRMOWRqT0ErUmczWEU2RnBackw0WThtWHpVbUxlbTh0a0RORHJ0TzhDL2pld2UrcTMwZ2M0TTluSmRnN25TMHpvZ3lzTi9HQjRkdWs3NEh4a3hqL2VMV1pjMWI5Sm9pOFIiLCJtYWMiOiIyNTBkMzAwMTljYzU2MGNiNmM4OGJiYTZjMjU4MTI4YTAyMDJmN2Y0OGYzMDVhNzg3NTRmZmY3NjBmOWIyZGI4IiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 14:52:02 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IldUZUFlbFp0ay8yNUlHUHZ1VXJ3eHc9PSIsInZhbHVlIjoiak42Y2hGR2pIcTV1UmtnSDZJZ0FqdTRkWDRlNUhiYVRMOWRqT0ErUmczWEU2RnBackw0WThtWHpVbUxlbTh0a0RORHJ0T" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlZoSCs5R2lxdXpMSGQ4R3UvMWlyV1E9PSIsInZhbHVlIjoiMXFMZWdGem12RXZYMGlnSjFwWkR0M1QreksrWkliaGxQWXFDZDZPdkt4ZllqbG1zT0FwTGNDeEh2VEY0d1VqdGs0UkVTbVlybHpadllSRWsyeW5aVFdac3k5Q1hqVHYwakcrejhWMS95OHBiUVp6OUtiUTBrd1ZpYm1nZ2Q3b3kiLCJtYWMiOiJhOWJhM2VhNWQwNzI3NDQ3MjU2MTY4NjBkZWY5ZmUwNGJlN2MzMjY2YzUyNjNkMWJiZDQ5YjkwZDA4ZjYyZWJlIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlZoSCs5R2lxdXpMSGQ4R3UvMWlyV1E9PSIsInZhbHVlIjoiMXFMZWdGem12RXZYMGlnSjFwWkR0M1QreksrWkliaGxQWXFDZDZPdkt4ZllqbG1zT0FwTGNDeEh" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldUZUFlbFp0ay8yNUlHUHZ1VXJ3eHc9PSIsInZhbHVlIjoiak42Y2hGR2pIcTV1UmtnSDZJZ0FqdTRkWDRlNUhiYVRMOWRqT0ErUmczWEU2RnBackw0WThtWHpVbUxlbTh0a0RORHJ0TzhDL2pld2UrcTMwZ2M0TTluSmRnN25TMHpvZ3lzTi9HQjRkdWs3NEh4a3hqL2VMV1pjMWI5Sm9pOFIiLCJtYWMiOiIyNTBkMzAwMTljYzU2MGNiNmM4OGJiYTZjMjU4MTI4YTAyMDJmN2Y0OGYzMDVhNzg3NTRmZmY3NjBmOWIyZGI4IiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 14:52:02 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IldUZUFlbFp0ay8yNUlHUHZ1VXJ3eHc9PSIsInZhbHVlIjoiak42Y2hGR2pIcTV1UmtnSDZJZ0FqdTRkWDRlNUhiYVRMOWRqT0ErUmczWEU2RnBackw0WThtWHpVbUxlbTh0a0RORHJ0T" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlZoSCs5R2lxdXpMSGQ4R3UvMWlyV1E9PSIsInZhbHVlIjoiMXFMZWdGem12RXZYMGlnSjFwWkR0M1QreksrWkliaGxQWXFDZDZPdkt4ZllqbG1zT0FwTGNDeEh2VEY0d1VqdGs0UkVTbVlybHpadllSRWsyeW5aVFdac3k5Q1hqVHYwakcrejhWMS95OHBiUVp6OUtiUTBrd1ZpYm1nZ2Q3b3kiLCJtYWMiOiJhOWJhM2VhNWQwNzI3NDQ3MjU2MTY4NjBkZWY5ZmUwNGJlN2MzMjY2YzUyNjNkMWJiZDQ5YjkwZDA4ZjYyZWJlIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlZoSCs5R2lxdXpMSGQ4R3UvMWlyV1E9PSIsInZhbHVlIjoiMXFMZWdGem12RXZYMGlnSjFwWkR0M1QreksrWkliaGxQWXFDZDZPdkt4ZllqbG1zT0FwTGNDeEh" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "WxUH0qAH3hdaoesU0afneRRSYIHfxepWJCGylzeW" "uc_cart_id" => "e037f12a05fec4862ade479061fd473d" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/8739" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 02:52:02GET/chapter/87391121912