Browsing by Subject "nanopartikkeli"

Posterior eye segment diseases, such as age-related macular degeneration, are leading causes of preventable visual impairment in the developed countries. Direct intravitreal injections are currently routinely used to deliver therapeutic agents most efficiently to posterior eye segment. Regular injections can however cause ocular complications and some drugs may also be toxic to ocular tissues at high local concentrations of free drug. Different nano-sized particulate systems have been extensively studied as possible drug delivery systems for intravitreal administration offering sustained, local drug action with controlled release. The vitreous gel can form a barrier for diffusion of particles due to its macromolecular structure and composition. Furthermore, ageing and different disease states cause changes in the vitreous structure possibly resulting in shift in the intravitreal movement of particulate systems. In the literature part of this Master's thesis ocular drug delivery is reviewed with main focus on drug targeting in the posterior eye segment. In the experimental work liposomes with different lipid compositions and surface charges were prepared as model particulate systems to evaluate the intravitreal diffusion of nanoparticles with confocal microscope. Furthermore, the influence of aging on the intravitreal diffusion was modeled by enzymatic degradation of the vitreous gel structure. It is discovered that vitreous gel hinders the movement of nanoparticles. Level of hindrance depends on particle's characteristics. 100-200 nm anionic particles move quite freely in the negatively charged vitreous gel. Similarly sized cationic particles are immobile in the vitreous due to electrostatic interactions between surface of the cationic particle and anionic glycosaminoglycans in the vitreous. 1 µm anionic and cationic particles are sterically trapped inside the vitreous meshwork created by the 3-dimensional biopolymer network of the vitreal macromolecules. Vitreous liquefaction increases the diffusion rate of nanoparticles but the clinical impact on ocular pharmacokinetics needs further research.

In cancer therapy nanocarriers can be loaded with therapeutic or diagnostic agent and nucleic acid sequences. Targeting moieties can be attached to the nanocarrier for passive or active targeting or carrier can be labeled with radioactive isotope for imaging or radiotherapeutic purposes. Enclosing the drug in a nanocarrier may improve the molecule's physico-chemical properties, bioavailability, reduce side-effects, longer the circulation time and dosing interval, and improve uptake in the target tissues. Thus, the efficacy of chemo- or radiotherapeutic could be improved. It may lead to improved survival. Pro gradu investigates nanocarriers' role in cancer therapy. Regardless of research, continued for decades, only 2 (Europe) or 3 (United States) nanoparticle formulations are approved in cancer therapy. Major limiations are inefficient uptake in the target tissue, immunogenicity of nanoparticles and targeting ligands, and lability. The aim of this study was to investigate pre-targeting of 99mTc-labeled, PEGylated and biotinylated liposomes into human ovarian adenocarcinoma cells in vitro and in mice in vivo. Targeting moiety used was biotinylated cetuximab (Erbitux®), an antibody that binds into EGF-receptors, over-expressed in these cells. Pre-targeting was compared to active one step-targeting, with antibody attached to liposomes, and passive targeting. Development of more accurate imaging techniques has accelerated the investigation of targeted nanoparticles. Molecular imaging enables real-time tracking of nanoparticle distribution and metabolic changes. In literature review, SPECT and PET imaging in cancer therapy and nanoparticle research, will be discussed. These imaging methods overcome challenges in sensitivity and accuracy, faced by other imaging methods. In this study we also investigated the biodistribution of 99mTc-labeled liposomes in mice using NanoSPECT-CT-device. Activity in tumor, spleen and liver was quantified using InVivoScope-software and gamma counter and these results were compared. In in vitro study, pre-targeting method was 2,7and 3,5-times more efficient compared to the liposome controls in SKOV3 and SKOV3.ip1 cell lines, respectively. Although, one-step targeting formulation targeted the cells even better. In in vivo -study, i.p.-administered liposomes distributed into tumor more efficiently compared to i.v.-administered liposomes. I.p. pre-targeting method was 1,24-fold more efficient compared to passive targeting, considering the % ID / g tissue. However, %ID/organ in pre-targeting method was 5,9 % whereas passive targeting reached the value of 5,4 %. Conclusively, the difference between pre-targeting and passive targeting was modest. InVivoScope and gamma counter quantification results didn't correlate. Further investigation is needed and protocol optimization required in targetin liposomes into tumors.