FUNCTIONALIZED CARBON NANOSTRUCTURES AS TEMOZOLOMIDE CARRIERS: PHYSICOCHEMICAL AND BIOPHARMACEUTICAL CHARACTERIZATION.

FUNKCIONALIZOVANE NANOSTRUKTURE UGLJENIKA KAO NOSAČI TEMOZOLOMIDA; FIZIČKOHEMIJSKA I BIOFARMACEUTSKA KARAKTERIZACIJA.

In this study, temozolomide (TMZ), a drug used in the treatment of anaplastic astrocytoma and glioblastoma multiforme, was incorporated in multiwalled carbon nanotubes (MWCNTs) and hybrid carbon nanotubes with graphene (MWCNTs-G) functionalized by polyethylene glycol (PEG). The aim was to evaluate the potential of these nanocarriers for targeted delivery and sustained release of TMZ in brain tumor cells. Oxidized MWCNTs and MWCNTs-G were noncovalently functionalized with PEGs of different molecular weights and subsequently loaded with TMZ following standard procedures. Thorough physicochemical and biopharmaceutical characterization of the TMZ-loaded carbon nanocarriers pointed to high encapsulation efficacy (up to 67%) and drug loading (up to 18% out of 25% theoretical value) and homogeneous particle size distribution, with zaverage (160 to 300 nm) and zeta potential (-31 to -21 mV) of the particles adequate for crossing the blood-brain-tumor-barrier (BBTB) and entering into the tumor cells. Successful functionalization and TMZ loading were confirmed by SEM and TEM images, UV-Vis absorption, infrared and Raman spectroscopy, and TGA analyses. Sustained release of TMZ from the carbon nanocarriers was observed in vitro. The presented findings form a fundamental platform for further investigation of these formulations against different types of glioma cells and in adequate animal models. [ABSTRACT FROM AUTHOR]

U ovom radu, temozolomid (TMZ), lek koji se koristi u lečenju anaplastičnog astrocitoma i multiformnog glioblastoma, ugrađen je u višeslojne ugljenične nanocevi (VSUNC) i hibridne ugljenične nanocevi sa grafenom (VSUNC-G) funkcionalizovanim polietilenglikolom (PEG). Cilj je bio da se proceni potencijal ovih nanonosača za ciljanu isporuku i produženo oslobađanje TMZ u c'elijama tumora mozga. Oksidovani VSUNC i VSUNC-G su nekovalentno funkcionalizovani sa PEG-ima različite molekulske mase i zatim je nanet TMZ prema standardnim procedurama. Temeljna fizičko-hemijska i biofarmaceutska karakterizacija nanonosača ugljenika sa nanetim TMZ ukazala je na visoku efikasnost inkapsulacije (do 67%) i punjenje lekom (do 18% od 25% teorijske vrednosti) i homogenu distribuciju veličine čestica, sa z-prosekom (160 do 300 nm) i zeta potencijala (-31mV do -21 mV) čestica adekvatnih za prelazak krvno-moždane-tumorske barijere i ulazak u tumorske c'elije. Uspešna funkcionalizacija i TMZ nanošenje potvrđeni su SEM i TEM slikama, UV-Vis apsorpcijom, infracrvenom i Raman spektroskopijom i TGA analizama. Produženo oslobađanje TMZ iz ugljeničnih nanonosača je zapaženo in vitro. Prikazani nalazi čine osnovnu platformu za dalje istraživanje ovih formulacija protiv različitih tipova c'elija glioma i na adekvatnim životinjskim modelima. [ABSTRACT FROM AUTHOR]