Tomasz Urbaniak
Wroclaw Medical University, Poland
Title: Lamivudine-poly-E-caprolactone conjugate based particles for targeted drug delivery, synthesis and characterization
Biography
Biography: Tomasz Urbaniak
Abstract
Poly-E-caprolactone (PCL) is biodegradable, nontoxic polyester synthesized mainly in ring-opening polymerization
(ROP) of E-caprolactone (CL). PCL alone or in blends was utilized in numerous medical applications, such as scaffolds,
implants, nano- and micro- drug carriers. It is characterized by slow degradation of polyester chains in hydrolytic mechanism.
Lamivudine (LV), as well as other antiretroviral drugs used in HIV-1 treatment, targets infected immune system cells, mainly
CD4+ T helper cells. However, other infected cells like macrophages, monocytes, dendritic cells are found through whole body,
including lungs and central nervous system. This cells halflife, measured in weeks/years, is dramatically longer in comparison
to CD4+ T helper cells, which is counted in hours/days. Such cells are often recognized as reservoirs of retroviruses, especially
these which are found in sites hardly available for drug substances, so called “sanctuaries”. The aim of this study was to design a
process of poly-E-caprolactone-lamivudine conjugate (PCL-LV) synthesis, and forming it into microspheres. Due to extremely
slow hydrolytic degradation, phagocytosis would be main mechanism of intravenously administered particles clearance.
Suggested mechanism of ROP includes formation of bond between initiator and polymer backbone. Drug bound covalently
to oligomeric chain would not be released from polymeric matrix in to plasma, therefore whole administered dose would
eventually achieve phagocytic cells, i.e., HIV-1 infected macrophages, monocytes or dendritics cells. Conjugate structure was
confirmed by the proton nuclear magnetic resonance and electro-spray ionization time of flight mass spectroscopy. Further
stage of study included microsphere forming in a variant of solvent evaporation method. Shape and size of obtained particles
was determined by scanning electron microscopy, light microscopy and dynamic light scattering. Average molecular weight of
obtained polymers was 5400 Da, size of prepared particles varied from nanometric to micrometric dimensions.