Kev Txhim Kho Ntawm Serine Modification-based raum-targeted Drug Delivery System

Kev xa cov tshuaj rau lub raum yog qhov tseem ceebkho mob raumlos ntawm kev txhim kho kev kho kom zoo thiab kev nyab xeeb. Txawm li cas los xij, kev tsom mus rau cov tshuaj rau lub raum yog qhov nyuaj, vim tias cov tshuaj nano-carriers feem ntau raug kaw los ntawm cov kab mob reticuloendothelial hauv daim siab thiab tus po. Tsis ntev los no, peb tau tshaj tawm tias serine-hloov polyamidoamine (Ser-PAMAM) dendrimer ua haujlwm zoo li muaj zog heev.lub raum-targeting tshuaj nqa. Tsis tas li ntawd, peb pom tau hais tias Ser-PAMAM feem ntau sau nyob rau hauv lub raum, tshwj xeeb tshaj yog nyob rau hauv proximal tubules, ib tug qauv txuam nrog pathogenesis ntawm lub raum kab mob thiab lub raum carcinoma hlwb. Tsis tas li ntawd, captopril tau ua tiav lub hom phiaj rau lub raum siv Ser-PAMAM, thiab cysteine- lossis S-nitrosothiol (qhov chaw ntawm nitric oxide)-loaded Ser-PAMAM zoo inhibit qhov tshwm sim ntawmmob raumraws li lub raumischemia/reperfusion. Hauv kev tshuaj xyuas no, peb tau sau tseg cov kev cov nyom tsis ntev los no hauv kev tsim ib qhotshuaj rau lub raum tsomkev xa khoom thiab sib tham txog kev siv hluav taws xob ntawm peb cov kev hloov kho serine-raws li kev txhim kho rau qhov system no kom ua tau zookho mob raum. 

Ntsiab lus:lub raum tshuaj tsom, serine, dendrimer, raum ischemia / reperfusion

NYEEM NTXIV RAU HAUV HNUB NYOOG CISTANCHE los tiv thaiv KIDNEY FUNCTION

1. Ua ntej tshaj plaws

Drug delivery system:

DDS) txhais tau tias yog ib qho system lossis thev naus laus zis uas ua tiav cov txiaj ntsig zoo ntawm cov tshuaj los ntawm kev tswj hwm lawv cov tshuaj pharmacokinetics. Tshwj xeeb, hom phiaj hom DDS, uas muaj txiaj ntsig zoo xa cov tshuaj mus rau cov chaw thiab cov hlwb, ua lub luag haujlwm tseem ceeb hauv kev txhim kho thiab siv cov tshuaj vim tias nws txuas ncaj qha rau kev kho mob thiab cov kev mob tshwm sim ntawm cov tshuaj. . 1) Tsis ntev los no tau txais kev pom zoo tshiab tus kab mob coronavirus 2019 (COVID-19) tshuaj tiv thaiv thiab lwm yam tshuaj nucleic acid, chimeric antigen receptor (CAR)-T therapy thiab antibody-drug conjugates rau kev kho mob qog noj ntshav hauv kev txhim kho cov tshuaj raws li kev tshawb nrhiav tshuaj tshiab modalities, xws li kev tshawb nrhiav tshuaj, DDS thev naus laus zis yog tus yuam sij rau nws cov kev siv tau. pom. 2) Tawm tsam keeb kwm yav dhau los no, lub luag haujlwm thiab qhov tseem ceeb ntawm DDS thev naus laus zis hauv kev txhim kho tshuaj yog nce ntxiv, thiab kev siv tshuab DDS tshiab raws li cov tswv yim tshiab yog xav tau.

Ntawm qhov tod tes, txawm tias tus naj npawb ntawmkab mob raumxws lilub raum cell carcinomathiabmob raum mobtau nce zuj zus nyob rau xyoo tas los no, kev txhim kho tshuaj tshiab tsis tau ua tiav thiab kev kho mob tseem ceeb tsis tau tsim, ua rau lawv cov kab mob uas tsis muaj kev xav tau kev kho mob siab. . . Tam sim no cov qauv kev kho mob rau lub raum cell carcinoma suav nrog cov tshuaj molecular lub hom phiaj thiab cov tshuaj tiv thaiv kab mob tiv thaiv kab mob, tab sis tseem muaj teeb meem xws li kev phiv los ntawm cov teeb meem pharmacokinetic. Ntawm qhov tod tes, muaj qee yam tshuaj muaj los kho mob raum mob, thiab raws li cov tsos mob hnyav zuj zus, uremia tshwm sim, yuam cov neeg mob mus rau kev lim ntshav dag. Txhawm rau txhim kho kev kho mob thiab kev ua neej zoo ntawm cov neeg mob lub raum, nws yog ib qho tsim nyog yuav tsum xa cov tshuaj kho mob mus rau lub raum kom zoo, uas yog lub hom phiaj, tshwj xeeb tshaj yog rau lub raum tubule, uas yog qhov chaw pib ntawm lub raum cell. carcinoma thiab mob raum mob. Kev tsim kho tshiab ntawm DDS thev naus laus zis yog qhov tseem ceeb.

Yog li ntawd, tsab xov xwm no yuav piav qhia txog qee qhov kev txhim kho hauv lub raum-targeting DDS kev tshawb fawb thiab qhia txog kev txhim kho lub raum-targeting DDS siv kev hloov kho serine, uas cov kws sau ntawv tsim nws tus kheej.

2. Txoj kev loj hlob ntawm lub raum-targeting DDS

Hais txog cov tshuaj tsom mus rau lub raum, nws tau ntev tau tshaj tawm tias cov tshuaj tau tsom mus rau lub raum siv cov tshuaj lysozyme zoo. Kev khi ntawm covtshuaj tiv thaiv kab mobnaproxen rau lysozyme tau pom tias yuav ua rau muaj kev nqus ntawm naproxen mus rau lub raum lub raum tubular epithelial hlwb tom qab glomerular filtration3,4). Nws yog xav tias uptake tshwm sim los ntawm electrostatic kev sib cuam tshuam thiab megalin receptors. Tsis tas li ntawd, succinic acid thiab aconitic acid, uas muaj cov nqi tsis zoo, yog lub npe hu ua lub raum tsom cov ntsiab lus rau kev xa cov tshuaj polymeric rau ob lub raum, tab sis succinic acid thiab aconitic acid-hloov polymers kuj raug xa mus rau lub raum, tab sis kuj mus rau daim siab. . Muaj teeb meem nrog rau lub raum selectivity. 5,6) Ntawm qhov tod tes, polyvinylpyrrolidone-raws li cov tebchaw tau nyiam yav dhau los ua cov polymers uas ua haujlwm zoo rau lub raum, tab sis lawv tseem tsis tau muab coj los siv. 7)

Tsis ntev los no, Williams et al. qhia particle diameters li ntawm 350-400 mm siv lub thaiv copolymer uas muaj polylactic-co-glycolic acid (PLGA) thiab polyethylene glycol (PEG). tau tshaj tawm tias polymeric micelles ntawm nm loj yog siv los ua cov khoom thauj khoom xa mus rau lub raum. 8) Nyob rau hauv vivo pharmacokinetic kev soj ntsuam siv ib qho hauv vivo imaging system tau pom tias polymeric micelles tsiv mus rau ob lub raum, txawm tias zoo. Tsis tas li ntawd, Deng et al. tau tshaj tawm tias siv cov micelles polymeric, cov tshuaj tiv thaiv kab mob triptolide tuaj yeem xa mus rau ob lub raum txhawm rau txhawm rau tiv thaiv ischemia-reperfusion raug mob. 9) Lub raum kev thauj mus los ntawm polymeric micelles yog qhov nyuaj vim hais tias cov particle loj ntawm polymeric micelles yog 350-400 nm, uas yog loj dua li molecular loj (10 nm los yog tsawg) uas yog lim los ntawm lub glomerulus. Ib qho kev xav tau raug pom zoo tias cuam tshuam nrog transcytosis los ntawm juxtatubular capillaries mus rau lub raum tubular epithelial hlwb es tsis yog reabsorption los ntawm lub raum tubules, tab sis cov ntsiab lus thiab lub hom phiaj efficiency rau lub raum tsis tau qhia meej. tsis muaj.

Ntxiv rau,lub raum tsomtau sim siv chitosan nanoparticles thiab liposomes li microparticulate formulations zoo ib yam li polymer micelles, tab sis feem ntau ntawm cov no muaj zoo pharmacokinetics zoo ib yam li cov saum toj no-hais PEG-PLGA polymer micelles. Txawm li cas los xij, cov ntsiab lus ntawm nws cov tshuaj pharmacokinetics, xws li covefficiency ntawm lub hom phiaj rau lub raum, nyob tsis meej. 10, 11) Nws.

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