Spontanoemulgujuće nanoemulzije za primenu kurkumina na koži: istraživanje uticaja međufaznih fenomena u koloidnom sistemu na efikasnost isporuke i biološku aktivnost

Abstract

U kontekstu biomedicinske primene, u poslednjih nekoliko decenija svedočimo svojevrsnojrenesansi koloidne nauke, što je verovatno posledica ekspanzije nanotehnologije i njene primene udomenu isporuke lekove, sa visoko postavljenim očekivanjima.Oslanjajući se na aktuelni trend istraživanja različitih nanonosača za isporuku aktivnih supstanci,cilj istraživanja ove doktorske disertacije bio je razvoj niskoenergetskih nanoemulzija zaunapređenu dermalnu isporuku kurkumina (model aktivne supstance), uz razumevanje složenihinterakcija koje su u osnovi nastanka ovih koloidnih sistema. Razmatrani su i određeni aspekatifizičkih i hemijskih modaliteta za poboljšanje isporuke aktivnih supstanci u/kroz kožu, sa idejom dase dizajnira prototip inovativnog adhezivnog flastera za dermalnu primenu koji će biti baziran nakombinaciji primene električne energije (kao fizičke metode za poboljšanje dermalneraspoloživosti), i nanoemulzija (naprednih nosača sa nanostrukturom).Kao rezultat eksperimentalnog rada, razvijene su visokobezbedne niskoenergetske nanoemulzijestabilisane kombinacijom polisorbata 80 i lecitina soje, sa trigliceridima srednje dužine lanca kaomasnom fazom, odnosno njihovom kombinacijom sa eukaliptolom ili pinenom (kao hemijskimpojačivačima penetracije). Primenom niza komplementarnih tehnika, detaljno su okarakterisane udomenu mikrostrukture, oblika, veličine i morfologije dispergovane faze, fizičke stabilnosti,bezbednosti primene i pogodnosti za očuvanje hemijske stabilnosti model aktivne supstance, što jebilo praćeno relevantnim biološkim i biofarmaceutskim ispitivanjima. Na samom kraju, pokazana jesuperiornonst primene adhezivnog sistema za jontoforezu u kombinaciji sa nanoemulzijom kaoinovativnog načina za dermalnu isporuku aktivnih supstanci.Kao najveći fundamentalni naučni doprinos ove doktorske disertacije može se smatrati analizafenomena na granici faza, otkrivanje doprinosa različitih ekscipijenasa koloidnoj stabilnosti, iproširenje savremene teorije o stabilizaciji nanoemulzija.

In the context of biomedical application, in the last few decades there has been a kind ofrenaissance of colloidal science, which is probably a consequence of the expansion ofnanotechnology and its application in the field of drug delivery, with highly posted expectations.Relying on the current research trend focused on different nanocarriers for the delivery of activepharmaceutical ingredients, the aim of this doctoral dissertation was to develop low-energynanoemulsions for improved dermal delivery of curcumin (a model active ingredient), with anunderstanding of the complex interactions that underlie the formation of these colloidal systems.Certain aspects of physical and chemical modalities for improvement of dermal drug deliveryinto/through the skin were considered, with the idea of designing a prototype of an innovativeadhesive patch for dermal application that will be based on a combination of electricity (as aphysical methods to improve dermal delivery), and nanoemulsions (advanced nanostructuredcarriers).The research resulted in the formation of highly safe low-energy nanoemulsions stabilized by acombination of polysorbate 80 and soybean lecithin, with medium-chain triglycerides as the oilphase, or their combination with eucalyptol or pinene (as chemical penetration enhancers). Using anumber of complementary techniques, they were thoroughly characterized in the context ofmicrostructure, shape, size and morphology of the dispersed phase, physical stability, safety andsuitability for maintaining chemical stability of the active ingredient, which was followed byrelevant biological and biopharmaceutical studies. Finally, the superiority of the application of theadhesive system for iontophoresis in combination with nanoemulsion as an innovative way fordermal delivery of active molecules has been shown.Extending the modern theory of nanoemulsion stabilization through the analysis of the interfacialphenomena, as well as the discovery of the contribution of various excipients to colloidal stability,could be considered as the most important scientific contributions of this doctoral dissertation.