| Abstract |
Efficient drug delivery to the ocular tissues faces several challenges due to the presence of several dynamic and static barriers, such as the blood–ocular barrier, tear formation andthelow permeability of the cornea. In addition,because of the very low drug bioavailability in the ocular area,repeated intraocular injections are required. Several nanomedicines have been formulated and evaluated for ocular drug delivery over the years, among which arepolymeric micelles, liposomes,hydrogels,polymer-drug and protein-drug conjugates[1].However,to the best of our knowledge, there are no examples of biodegradable systems, comprising materials which are approved by the Food and Drug Administration (FDA), beingalso capable of slowing down the release profile of drug, reported in the literature. Hence, the development of drug delivery systems that can ensureasuitable drug concentration for a prolonged time in different ocular tissues is certainly of great importance.In the present thesis, we aimed to develop polymeric nanocarriers for the encapsulation and delivery of Flurbiprofen, a nonsteroidal anti-inflammatory drug sold inthe market in the form of asolution under thebrand names Ocufen® and Ocuflur®.In the first part of this thesis, amphiphilic poly(ethylene glycol)-block-poly(l-lactide)(PEG-b-PLLA)diblock and PLLA-b-PEG-b-PLLA triblockcopolymers were synthesized with differentdegrees of polymerizationranging from 66 to 333. For the polymer synthesis, the ring-opening polymerization of the hydrophobic monomer l-lactide was used [2].The polymerization was carriedoutin the presence of stannous octoate (Sn(Oct)2) as the catalyst. Ring-opening polymerization (ROP) is a typeof chain-growth polymerization in which the terminus of thepolymer chain attacks the cyclic monomer to form longer polymerchains. The successful synthesis of the polymers wasverified by gel permeation chromatography (GPC) whereas their composition was determined byproton nuclear magnetic resonance (1HNMR)spectroscopy. 2In the second part of this thesis, the amphiphiliccopolymers were self-assembled in water to form either micellar or vesicular structures, able to encapsulate small hydrophobic molecules [3].Therefore, nanocarriers with two different methods were prepared. The first method includes thedissolution of the polymer in an organic solvent followed by the dropwise addition of the aqueous phase. In the second technique, the thin-film hydration method was used. In this process,the polymer is dissolved in an organic solvent followed by the evaporation of the solvent and the formationof a polymeric film.The film is then hydrated resulting in the self-assembly of the polymeric chains.The size of the nanoparticles was determined by dynamic light scattering (DLS) and their morphology was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Next, the release profile of a model dye, Sudan Red, loaded within the nanoparticles to simulate thehydrophobic drug, was studied.The release kinetics were monitored by UV/Vis spectroscopy. The experimental resultsshowed a slowerreleaseof Sudan Red, from mixed diblock and triblock copolymer micelles, reaching a 60% release after 14 days.
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