Paklitaksel - od biljke do lijeka

professional thesis

• Author: Petra Pejković
• Mentor: Sanda Vladimir-Knežević (mentor)
• Committee member: Jelena Filipović-Grčić (predsjednik povjerenstva)
• Committee member: Sanda Vladimir-Knežević (član povjerenstva)
• Committee member: Dubravko Jelić (član povjerenstva); MBZ: 301280
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2016, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Bioaktivne tvari biljnog podrijetla dragocjen su ishodni materijal za razvoj novih lijekova. Brojna znanstvena istraživanja usmjerena su otkrivanju novih lijekova antitumorskog djelovanja budući da je karcinom rastući svjetski zdravstveni problem i drugi glavni uzrok smrtnosti nakon kardiovaskularnih bolesti. Paklitaksel je otkriven upravo u sklopu jednog takvog znanstvenog projekta u kori pacifičke tise (Taxus brevifolia Nutt.).Danas je paklitaksel dio standardne terapije u liječenju različitih vrsta karcinoma, bilo u početnom ili u znapredovalom stadiju. Odobrene terapijske indikacije obuhvaćaju karcinom dojke, jajnika i pluća te Kaposijev sarkom povezan s AIDS-om. Cilj ovog specijalističkog rada bio je prikupiti i obraditi relevantna znanstvena istraživanja te pružiti pregled odnosa molekulske strukture i djelovanja paklitaksela, biosintetskog i sintetskog puta dobivanja, mehanizma djelovanja te farmakokinetičkog i kliničkog profila. Posebna pozornost posvećena je razumijevanju mehanizama rezistencije na paklitaksel i neželjenih učinaka, što je veliki poticaj razvoju suvremenih formulacija lijeka povećane selektivnosti i djelotvornosti te smanjenih toksičnih učinaka. U razvoju novih formulacija paklitaksela najčešće se koriste nanočestice, liposomi, ciklodekstrini, analozi teprolijekovi. Dosadašnje znanstvene spoznaje ukazuju na velik potencijal primjene novih formulacija paklitaksela te potiču buduća istraživanja.

Abstract (english)

Bioactive substances derived from plants are a valuable source of medicines. Numerous scientific research projects are focused on discovery of new anticancer agents since cancer is a growing world health problem and the second major cause of death after cardiovascular diseases. In one such scientific project paclitaxel was discovered as the major substance in the bark of pacific yew (Taxus brevifolia Nutt.). Today paclitaxel is a standard therapy in the treatment of different types of carcinoma, both in early and advanced stages. It is approved for treatment of breast cancer, ovarian cancer, lung cancer and AIDS-related Kaposi's sarcoma. The aim of this work was to collect and analyse the relevant scientific research and give overview of molecular structure and activity relationship of paclitaxel, biosynthetic and synthetic pathways, mechanism of action, pharmacokinetic and clinical profiles. Special focus was put on understanding of resistance mechanisms to paclitaxel as well as adverse events which are the important impulses for development of new formulations with enhanced selectivity and efficiency, and reduced toxic effects. The most used approaches for developing new formulations of paclitaxel are nanoparticles, liposomes, cyclodectrins, analogues and prodrugs. Current scientific data indicate a great potential for the use of new paclitaxel formulations and encourage further research.

• Keywords: paklitaksel; pacifička tisa; karcinom; Taxus brevifolia Nutt.
• Keywords (english): paclitaxel; pacific yew; cancer; Taxus brevifolia Nutt.
• Language: croatian
• URN:NBN: urn:nbn:hr:163:533533
• Study programme: Title: Drug development; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni magistar/sveučilišna magistra razvoja lijekova (sveučilišni magistar/sveučilišna magistra razvoja lijekova)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-01-13 10:01:36