Nanotherapeutics for the Treatment of Hepatocellular Carcinoma

Nanoformulations and Their Therapeutic Advantages

Author(s): D. Nedra Karunaratne*, Thusini D. Wijerathne, Nuwanthi P. Katuwavila and Geethi K. Pamunuwa

Pp: 123-165 (43)

DOI: 10.2174/9789815039740122010005

* (Excluding Mailing and Handling)

Abstract

Cancer therapy involves nanomedicine, which can provide a plethora of
advantages unattainable via conventional medicine as the materials of nano-level
exhibit unique physicochemical and biological properties. Both cancer therapy and
cancer therapy research utilize nanoformulations based on liposomes, polymeric
nanoparticles, solid lipid nanoparticles, metal nanoparticles, dendrimers, and
nanoemulsions for facilitating high specificity negating off-target toxicity, prolongedrelease
maintaining drug concentration and reducing dosing frequency, increased
solubilization and absorption, and penetration of impermeable barriers. The entrée to
this chapter is thus made with a brief description of nanomedicine, which is followed
by a description of the designing of nanoformulations for therapeutics. Explanations on
the types and advantages of nanoformulations are also given. The second section of the
chapter describes nanoformulations as therapeutics for cancer, explaining the different
targeting strategies and novel approaches involving nanoparticles. Like numerous other
cancers, nanoformulations are researched extensively in therapy for hepatocellular
carcinoma, the second leading cause of cancer-related deaths. The final section of the
chapter deals with the therapeutic advantages of nanoformulations in hepatocellular
carcinoma. The prominent nanomaterials investigated in hepatocellular carcinoma
therapy include nanoparticles of biopolymers, nanoparticles of artificial biodegradable
polymers, metallic nanoparticles, carbon nanotubes, and mesoporous nanoparticles.
Targeting of drug-loaded nanoparticles is achieved in therapy for hepatocellular
carcinoma via passive targeting and/or active targeting. A key milestone in
hepatocellular carcinoma therapy is the approval of the drug Zinostatin stimalamer, an
emulsion-based formulation, by the Japanese Ministry of Labour, Health, and Welfare.


Keywords: Active targeting, Bioavailability, Biodegradable, Cancer, Chemotherapy, Controlled release, Dendrimers, Emulsions, Hepatocellular carcinoma, Immunoliposomes, Liposomes, Metal nanoparticles nanoformulations, Nano-medicine, Nanoparticles, Passive targeting, Polymeric nanoparticles, Solid lipid nanoparticles, Therapeutics, Targeted delivery.

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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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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 <= 51595851 and j.to_ip >=51595851 )) and ((j.from_date <= 1739988353 and j.to_date >= 1739988353 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16542) 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 <= 51595851 and j.to_ip >=51595851 )) and ((j.from_date <= 1739988353 and j.to_date >= 1739988353 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16542) 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 <= 51595851 and j.to_ip >=51595851 )) and ((j.from_date <= 1739988353 and j.to_date >= 1739988353 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16542)
      520μsalphaeurekaselec_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` = 3312 and `b`.`banner_from_date` <= 1739988353 and `b`.`banner_to_date` >= 1739988353 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.02msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3312
      • 3: 1739988353
      • 4: 1739988353
      • 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='b1a546aa802f9e1615609e3117b08f4c'
      230μsalphaeurekaselec_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
    19Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        QcTPxOjQlFMSQ3AvAqHO8uwpBsxDEGqulqS1MKfw
        uc_cart_id
        b1a546aa802f9e1615609e3117b08f4c
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16542" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/16542
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IkNwZDVlRm8vUlQ5VW5KdVRuVEVNTnc9PSIsInZhbHVlIjoiWDZYV1N2RTE2dnBGbmpUVk5OOFpYa0p6TEJ5ZUJibzRUcTRyTnJaeVRWRT0iLCJtYWMiOiI1NWYxNWVmY2U3OWJlODM3YTI0NzNmNTkwOGQzZWYxOTYzNjU5MWM4MTMyMmM1ZGM3MmNkNDBjY2ZiNjgxNjM5IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IkNwZDVlRm8vUlQ5VW5KdVRuVEVNTnc9PSIsInZhbHVlIjoiWDZYV1N2RTE2dnBGbmpUVk5OOFpYa0p6TEJ5ZUJibzRUcTRyTnJaeVRWRT0iLCJtYWMiOiI1NWYxNWVmY2U3OWJl" ] "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
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        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 => "Wed, 19 Feb 2025 18:05:53 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IitKWnNockRvUk40VVlQK2t4QkJHRnc9PSIsInZhbHVlIjoiL2JJTlFWTWprdEcyNzIzRlVQL0FRZklXM0xVWGp5Ym56OEd6M1dsNjR3eGlCY3MzTTFCa09TVWRTcFdRRlpuUGh0YjB4Mk1XVVJqdUZ1eStZTWZ1M2lkVGhkeU45WnFUMXhONFBreUxhd1dTcUVkRVF0N2JPamwvTmZZWDBZZlUiLCJtYWMiOiI4OWIzNmZlZGNjZTQ1ZWVlZDk5OGE5NWQ4MDE3YzhlYzhjZTBhYmY5YjFjOGUyOTNlOTQ0ODdmMDFmODQ4YTk1IiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:05:53 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IitKWnNockRvUk40VVlQK2t4QkJHRnc9PSIsInZhbHVlIjoiL2JJTlFWTWprdEcyNzIzRlVQL0FRZklXM0xVWGp5Ym56OEd6M1dsNjR3eGlCY3MzTTFCa09TVWRTcFdRRlpuUGh0YjB4M" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkxIcG9wNWtYc1dGMENWOTMvTlgyeWc9PSIsInZhbHVlIjoiNU0rc0Q4ejkxM0VBT2dtRTJOSG9EVDVjL1g1OGNwcjhrdi94d1JIYks0OWlXWEN1LzYwWUdnWi9lNUdTcUcvd0NEb1JDWDUzQmp1N0hleElZZDZ5ZXNzeURtUmVkc3JEblZSMFBYQ2o5QUpqMlRxVWs2OHF1K0R5SG9KNnREMGsiLCJtYWMiOiI1YmNjMzBiYjg0YjA0ZjNjMmUzMTcyNzYxZjBlYjRhMzMwYThiYWYzYjcyZWI5NGJkNDNjMDY4NzIxYmVlMzZmIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkxIcG9wNWtYc1dGMENWOTMvTlgyeWc9PSIsInZhbHVlIjoiNU0rc0Q4ejkxM0VBT2dtRTJOSG9EVDVjL1g1OGNwcjhrdi94d1JIYks0OWlXWEN1LzYwWUdnWi9" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IitKWnNockRvUk40VVlQK2t4QkJHRnc9PSIsInZhbHVlIjoiL2JJTlFWTWprdEcyNzIzRlVQL0FRZklXM0xVWGp5Ym56OEd6M1dsNjR3eGlCY3MzTTFCa09TVWRTcFdRRlpuUGh0YjB4Mk1XVVJqdUZ1eStZTWZ1M2lkVGhkeU45WnFUMXhONFBreUxhd1dTcUVkRVF0N2JPamwvTmZZWDBZZlUiLCJtYWMiOiI4OWIzNmZlZGNjZTQ1ZWVlZDk5OGE5NWQ4MDE3YzhlYzhjZTBhYmY5YjFjOGUyOTNlOTQ0ODdmMDFmODQ4YTk1IiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:05:53 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IitKWnNockRvUk40VVlQK2t4QkJHRnc9PSIsInZhbHVlIjoiL2JJTlFWTWprdEcyNzIzRlVQL0FRZklXM0xVWGp5Ym56OEd6M1dsNjR3eGlCY3MzTTFCa09TVWRTcFdRRlpuUGh0YjB4M" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkxIcG9wNWtYc1dGMENWOTMvTlgyeWc9PSIsInZhbHVlIjoiNU0rc0Q4ejkxM0VBT2dtRTJOSG9EVDVjL1g1OGNwcjhrdi94d1JIYks0OWlXWEN1LzYwWUdnWi9lNUdTcUcvd0NEb1JDWDUzQmp1N0hleElZZDZ5ZXNzeURtUmVkc3JEblZSMFBYQ2o5QUpqMlRxVWs2OHF1K0R5SG9KNnREMGsiLCJtYWMiOiI1YmNjMzBiYjg0YjA0ZjNjMmUzMTcyNzYxZjBlYjRhMzMwYThiYWYzYjcyZWI5NGJkNDNjMDY4NzIxYmVlMzZmIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkxIcG9wNWtYc1dGMENWOTMvTlgyeWc9PSIsInZhbHVlIjoiNU0rc0Q4ejkxM0VBT2dtRTJOSG9EVDVjL1g1OGNwcjhrdi94d1JIYks0OWlXWEN1LzYwWUdnWi9" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "QcTPxOjQlFMSQ3AvAqHO8uwpBsxDEGqulqS1MKfw" "uc_cart_id" => "b1a546aa802f9e1615609e3117b08f4c" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16542" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:05:53GET/chapter/165421121921