Ua raws li peb cov txheej txheem dhau los txhais FDA cov ntsiab lus, cov txheej txheem kev tswj hwm thiab kev nyab xeeb rau cov khoom lag luam microneedle, ntau tus kws tshaj lij kev lag luam tau ncav cuag los qhia cov kev soj ntsuam uas FDA cov cai tswj hwm rau microneedles tau ua rau muaj kev cuam tshuam rau cov khoom lag luam hauv tsev hauv Suav teb. Feem ntau cov khoom siv hauv tsev Class II hlau microneedle tau sau npe nyob rau hauv cov koob dov (20-03-05), ib pawg ntawm cov cuab yeej siv kho mob hauv Suav teb hauv Classification Catalog of Medical Devices. Qee cov khoom lag luam tau sau npe nyob rau hauv lub npe "microneedle transdermal thaj", kuj ua raws li kev tswj hwm txoj hauv kev rau cov khoom siv kho mob suav tshuaj.

Ntau tus nyeem tau hais txog ib leeg-crystal-silicon microneedles tsim tawm txawv teb chaws. Ib yam khoom tsim los ntawm NanoPass (Israel) tau txais Tuam Tshoj ntshuam Class III cov cuab yeej kho mob pom zoo xyoo 2019, sawv cev rau ib qho ntawm ob peb cov khoom lag luam muaj ib leeg-crystal-silicon microneedle khoom thoob ntiaj teb. Cov cuab yeej no tau raug tshem tawm los ntawm FDA hauv 2009 raws li Class II cov cuab yeej kho mob raws li kev lag luam npe MicronJet 600, raug xaiv los uaib leeg-lumen intradermal koob. Nws daim ntawv lub cev sib txawv ntawm cov tshuaj pleev ib ce microneedles paub rau pej xeem; functionally nws zoo li ib tug luv-needle intradermal injector. Thaum lub sij hawm FDA 510 (k) tshem tawm, cov tshuaj intradermal ib txwm siv los ntawm Terumo thiab BD raug xaiv los ua cov khoom siv los ua kom pom qhov sib npaug ntau.

Hauv kev soj ntsuam-kev tshawb fawb lub voj voog, cov lus tshuaj xyuasMicroneedle-enabled therapeutics xa thiab biosensing hauv kev sim tshuaj(DOI: 10.1016/j.joonrel.2023.07.023) yog thawj qhov kev tshuaj xyuas tshwj xeeb tshwj xeeb rau kev kuaj mob microneedle. Kos cov kev nkag siab tseem ceeb los ntawm cov ntawv tshaj tawm no, kab lus no qhia txog cov txheej txheem kev kawm, cov xwm txheej kho mob, cov kev tshawb pom tseem ceeb thiab kev lag luam tiam sis ntawm microneedles tshawb xyuas hauv kev tshawb fawb soj ntsuam.

Microneedle-Enabled Therapeutics Delivery and Biosensing in Clinical Trials

Abstract

Microneedles (MNs) yog micron-scale protrusion arrays kev koom ua ke rau ntau hom khoom siv platforms. Lawv tau kawm dav dav rau kev kho tus me nyuam nrog rau hauv-vivo thiab ex-vivo biosensing. Tau txais txiaj ntsig los ntawm cov txiaj ntsig tseem ceeb suav nrog kev tswj hwm tsis muaj qhov mob me me, muaj peev xwm rau kev thov tus kheej, thiab kev sib raug zoo nrog ntau yam kev kho mob them nqi, microneedles tuav cov lus cog tseg zoo rau kev xa tshuaj hauv zos thiab hauv lub cev. Qhov kev tshuaj xyuas no qhia txog cov kev sim tshuaj microneedle thoob ntiaj teb tau pib txij li xyoo 2007. Cov khoom siv microneedle kuaj tau muab faib ua tsib pawg: hollow microneedle, microneedle thaj ua rau thaj, xov tooj cua zaus microneedles, microneedle rollers thiab lwm yam tshwj xeeb microneedles. Kev tshuaj xyuas kev ua haujlwm tau ua tiav suav nrog kev teeb tsa microneedle, sijhawm sim sijhawm thiab thaj chaw faib khoom.

Ntsiab lus: microneedles; kev sim tshuaj; kev xa tshuaj; tshuab kuaj mob; kev kho tshiab; cov ntaub ntawv polymeric

Taw qhia

Microneedles yog micron-scale protrusions feem ntau ntau pua micrometers ntev. Lawv tuaj yeem ntsia tau rau ntawm cov chais, cwj mem-hom kev kho mob, thaj chaw substrates lossis cov koob txhaj tshuaj. Lawv cov txheej txheem tseem ceeb tso siab rau tsim ntau cov microchannels nyob rau hauv cov tawv nqaij barrier los pab txhawb kev nkag mus ntawm cov tshuaj kho mob rau hauv cov txheej txheem ntawm daim tawv nqaij; Qee cov qauv tsim tuaj yeem ua tiav cov tshuaj nkag ncaj qha rau hauv cov kab ke. Tus cwj pwm los ntawm qhov tsis tshua muaj mob profile, kev ua haujlwm yooj yim, kev siv tau hauv tsev thiab kev nyab xeeb zoo, ntau lub microneedle cov cuab yeej tau ua tiav kev soj ntsuam kuaj thiab ua tiav kev lag luam.

Txoj kev tshawb no tshawb fawb pej xeem ClinicalTrials.gov cov ntaub ntawv thiab txheeb xyuas 127 qhov kev sim tshuaj ntsuam xyuas ncaj qha ntsig txog microneedle technology. Cov cuab yeej kuaj tau muab faib ua tsib pawg: hollow microneedles, microneedle thaj ua rau thaj, xov tooj cua zaus microneedles, microneedle rollers thiab lwm yam microneedles. Hollow microneedles yog ntxiv subdivided rau hauv micro-injection thiab non-injection biosensing hom; microneedle-based thaj ua rau thaj ua rau thaj ua rau thaj ua rau thaj ua rau thaj ua rau thaj ua rau thaj ua rau thaj chaw, cov thaj ua rau thaj ua rau thaj thiab cov thaj ua rau thaj chaw liab qab tsuas yog siv rau kev kho mob ua ntej ntawm daim tawv nqaij.

Pawg ntawm Microneedles Deployed nyob rau hauv kev sim tshuaj

2.1 Hollow Microneedles

Hollow microneedles sawv cev rau qhov feem ntau siv cov qauv hauv kev sim tshuaj, suav txog 33.6% ntawm tag nrho cov kev tshawb fawb. Lawv muab faib ua micro-injection thiab non-injection biosensing variants raws li kev siv.

Micro-injection hom: xa ntau hom tshuaj kho mob intradermally rau hauv cov chaw cov ntaub so ntswg;

Hom tsis txhaj tshuaj: Feem ntau yog rau kev ntsuas cov kua dej sib txuas kom ua kom muaj kev cuam tshuam tsawg kawg nkaus ntawm biomarkers.

Cov khoom siv sawv cev: MicronJet 600 tsim los ntawm NanoPass Technologies (Israel). Nws yog ib qho khoom siv tsis muaj menyuam uas siv tau nrog peb 600 μm ib leeg-crystal-silicon hollow microneedles, sib haum nrog kev tswj hwm ntawm txhua cov tshuaj pom zoo rau kev txhaj tshuaj intradermal.

Daim ntawv thov kev kho mob tseem ceeb

Kev xa tshuaj tiv thaiv: Ib qho kev sim (NCT01304563) ua los ntawm University of Hong Kong tau txhaj tshuaj tiv thaiv kab mob khaub thuas trivalent ntawm MicronJet 600, lees paub qhov kev nyab xeeb zoo thiab kev tiv thaiv kab mob.

Kev xa cov tshuaj insulin: Kev tshawb fawb los ntawm Emory University Diabetes Center pom tau hais tias hollow microneedles tuaj yeem ua tau zoo thiab tsis muaj mob intradermal insulin xa rau menyuam yaus thiab cov tub ntxhais hluas uas muaj hom 1 mob ntshav qab zib mellitus.

Kev kho qhov muag: SCS Microinjector® tsim los ntawm Clearside Biomedical ntiav cov hollow microneedles los txhaj triamcinolone acetonide ncua kev kawm ntawv rau hauv qhov chaw suprachoroidal rau kev kho mob ntawm cov kab mob posterior-segment inflammatory xws li uveitis.

2.2 Microneedle Patches

• 2.2.1 Dissolvable microneedle thaj ua rau thaj

Fabricated los ntawm hydrophilic polymers. Thaum nkag mus rau ntawm daim tawv nqaij, koob cov lus qhia yaj hauv zos thiab tso cov tshuaj ntim rau hauv cov ntaub so ntswg.

Kev sim tshuaj tiv thaiv kab mob khaub thuas (NCT02438423) coj los ntawm Emory University siv thaj chaw nqa 100 dej-soluble polymer microneedles ntawm 650 μm ntev.

SkinJet tau ua qhov kev sim tshuaj ntsuam xyuas (NCT03646188) tshawb xyuas doxorubicin-loaded dissolvable microneedle thaj ua rau thaj chaw kho mob basal-cell carcinoma.

• 2.2.2 Coated microneedle thaj ua rau thaj

Non-dissolvable substrates nrog cov tshuaj kho mob coated rau cov lus qhia microneedle.

Qtrypta™ (M207), microneedle thaj rau kev kho mob migraine mob, muaj 1987 titanium microneedles txhua 340 μm ntev.

Abaloparatide-coated microneedle thaj ua rau thaj yog tshawb nrhiav rau kev kho transdermal ntawm postmenopausal osteoporosis.

• 2.2.3 liab qab microneedle thaj ua rau thaj

Nqa tsis payload lawv tus kheej. Lawv yog tsim los rau cov tawv nqaij ua ntej kev kho mob nkaus xwb, tsim microchannels los txhim kho daim tawv nqaij permeability ntawm cov tshuaj pleev ib ce tom ntej. 3M Microchannel Skin System (MSS) tau nthuav tawm kev nyab xeeb zoo heev thiab muaj kev zam txim rau ntau yam kev tshawb fawb soj ntsuam.

2.3 Xov tooj cua zaus (RF) Microneedles

RF zog (3 kHz-300 GHz) yog xa mus rau hauv lub dermis los ntawm microneedle electrodes los induce dermal coagulation thiab ua rau collagen remodeling, feem ntau yog siv nyob rau hauv zoo nkauj rejuvenation thiab caw caws pliav.

Endymed PRO Intensif handpiece tau txais FDA clearance rau lub ntsej muag aesthetic indications.

Lutronic Infini yog nruab nrog 49-pin sib hloov cartridge nrog insulated kub-plated microneedles xa cov xov tooj cua zaus zog. Hloov pauv tau cov cartridges ntawm ntau qhov sib txawv hloov mus rau qhov mob ntawm qhov sib txawv.

2.4 Microneedle Rollers

Handheld roller-type devices nrog stainless-steel microneedles mounted rau ntawm cov menyuam nruas, haum rau kev kho cov tawv nqaij loj. MTS Cov Menyuam ™ system los ntawm Clinical Resolution Laboratory muab ntau yam koob-ntev specifications xws li 0.2 hli txog 2.0 hli thiab tau siv dav hauv cov tawv nqaij-kho-tsim kev sim tshuaj.

Txoj Kev Pom Zoo hauv Microneedle Clinical Trials

3.1 Statistical profiles ntawm kev sim tshuaj

• Kev faib tawm ntawm thaj chaw: Tebchaws Asmeskas tau tuav cov kev sim tshuaj microneedle ntau tshaj plaws (57 txoj kev tshawb fawb), ua raws li Europe thiab East Asia.
• Lub sij hawm evolution: Lub ntiaj teb thawj microneedle kuaj sim tau pib hauv 2007; tus naj npawb txhua xyoo ntawm kev sim siab tshaj plaws hauv 2018.
• Devices parameters: Qhov nruab nrab ntawm microneedle ntev sib txawv ntawm cov qauv; RF microneedles muaj qhov ntev tshaj plaws nruab nrab ntev ntawm kwv yees li 1560 μm.

3.2 Cov lus qhia siv tshuaj kho mob

• Kev xa tshuaj: me-molecule chemicals, peptide thiab protein therapeutics, cell-based npaj thiab lwm yam;
• Kev txhaj tshuaj: Intradermal kev tshawb fawb txog kev mob khaub thuas, COVID-19, qhua pias, polio thiab lwm yam tshuaj tiv thaiv;
• Biosensing: minimally-invasive real-time saib xyuas ntawm in-vivo analytes xws li penicillin, lactose thiab levodopa.

Xaus

Ua tsaug rau nws qhov tsawg-invasive xwm thiab cov neeg siv-phooj ywg ua haujlwm, microneedle technology qhia tau hais tias dav dav hauv kev kho mob, tshuaj tiv thaiv thiab minimally-invasive biosensing. Technical bottlenecks tseem nyob. Cov kev tshawb fawb yav tom ntej muaj xws li kev txhim kho cov tshuaj-loading peev thiab optimization ntawm wearability thiab real-time analytical kev ua tau zoo rau wearable microneedle-raws li sensors. Kev lag luam FDA-nrawm cov khoom siv microneedle rau hnub no suav nrog MicronJet 600, SkinPen® Precision System thiab MTS Roller™ series.