Biodistribution of Polymer-Drug Conjugates in vivo
Author
Ziemczonek, Piotr Kacper
Term
4. term
Education
Publication year
2019
Submitted on
2019-09-10
Pages
83
Abstract
Polymer–drug conjugates hold promise for improving therapeutic efficacy and safety, but their in vivo biodistribution is critical to clinical performance. This thesis reviews core pharmacokinetic concepts of ADME, membrane transport and transporters, the blood–brain barrier, and plasma protein binding, and relates them to nanomedicine. The objective is to characterize the in vivo distribution of polymer–drug conjugates in rats using fluorescence‑based readouts. Following dosing, tissues were collected, cryosectioned, and examined by fluorescence microscopy (including confocal and two‑photon) for qualitative mapping, and by image analysis and spectrofluorimetry for relative and absolute quantification. The workflow includes calibration curves to convert signal to concentration, correction for tissue autofluorescence, and assessment of spatial correlation between cell nuclei and conjugate signal across organs such as brain, liver, lung, spleen, kidney, and a control paw sample. Specific quantitative and organ‑level findings are not reported in this excerpt, but the described experimental and analytical pipeline provides a practical basis for estimating tissue distribution and supporting pharmacokinetic interpretation and the future design of polymer–drug conjugates.
Polymer‑lægemiddelkonjugater kan forbedre behandlingers effektivitet og sikkerhed, men deres fordeling i kroppen (biodistribution) er afgørende for den kliniske effekt. Denne afhandling gennemgår de farmakokinetiske grundprincipper for ADME, membrantransport og transportører, blod‑hjerne‑barrieren samt plasmaproteinbinding og sætter det i relation til nanomedicin. Formålet er at karakterisere in vivo‑fordelingen af polymer‑lægemiddelkonjugater i rotter ved hjælp af fluorescensbaserede metoder. Efter dosering blev væv udtaget, kryosnittet og analyseret med fluorescensmikroskopi (bl.a. konfokal og to‑foton) for kvalitativ kortlægning, og med billedanalyse og spektrofluorimetri for relativ og absolut kvantificering. Arbejdet omfatter kalibreringskurver til omregning af signal til koncentration, korrektion for vævsautofluorescens og vurdering af rumlig sammenhæng mellem cellekerner og konjugatsignal på tværs af organer som hjerne, lever, lunge, milt, nyre og en kontrolpote. Det konkrete datasæt og organ‑specifikke resultater er ikke indeholdt i dette uddrag, men den beskrevne forsøgs‑ og analysepipeline giver et praktisk grundlag for at vurdere vævsfordeling og understøtte tolkning af farmakokinetik og videre design af polymer‑lægemiddelkonjugater.
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Keywords