Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4

Search results for: bioconjugate

4 Hyaluronic Acid as Potential Excipient for Buccal Delivery

Authors: Flavia Laffleur

Abstract:

Summary: Biomaterials have gained immense interest in the pharmaceutical research in the last decades. Hyaluronic acid a carbohydrate and mucopolysaccharide was chemically modified in order to achieve and establish a promising platform for buccal drug delivery. Aim: Novel biomaterial was tested for its potential for buccal drug delivery. Background: Polysaccharide hyaluronic acid (HA) was chemically modified with cysteine ethyl ether (CYS). By immobilization of the thiol-bearing ligand on the polymeric backbone the thiolated bioconjugate HA-CYS was obtained. Methodology: Mucoadhesive, permeation enhancing and stability potential as well as mechanical, physicochemical properties further mucoadhesive strength, swelling index and residence time were investigated. The developed thiolated bioconjugate displayed enhanced mucoadhesiveness on buccal mucosa as well as permeation behavior and polymer stability. The near neutral pH and negative cytotoxicity studies indicated their non-irritability and biocompatible nature with biological tissues. Further, the model drug sulforhodamine 101 was incorporated to determine its drug release profiles. Results: The synthesized thiomer showed no toxicity. The mucoadhesion of thiolated hyaluronic acid on buccal mucosa was significantly improved in comparison to unmodified one. The biomaterial showed 2.5-fold higher stability in polymer structure. The release of sulforhodamine in the presence of thiolated hyaluronic acid was 2.3-fold increased compared to hyaluronic acid. Conclusion: Thus, the promising results encourage further investigations and exploitation of this versatile polysaccharide. So far, hyaluronic acid was not evaluated for buccal drug delivery.

Keywords: buccal delivery, hyaluronic acid, mucoadhesion, thiomers

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3 Nanotechnology-Based Treatment of Klebsiella pneumoniae Infections

Authors: Lucian Mocan, Teodora Mocan, Matea Cristian, Cornel Iancu

Abstract:

We present method of nanoparticle enhanced laser thermal ablation of Klebsiella pneumoniae infections, using gold nanoparticles combined with a specific growth factor and demonstrate its selective therapeutic efficacy. Ab (antibody solution) bound to GNPs (gold nanoparticles) was administered in vitro and determined the specific delivery of the nano-bioconjugate into the microorganism. The extent of necrosis was considerable following laser therapy, and at the same time, normal cells were not seriously affected. The selective photothermal ablation of the infected tissue was obtained after the selective accumulation of Ab bound to GNPs into bacteria following perfusion. These results may represent a major step in antibiotherapy treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, Klebsiella pneumoniae, nanoparticle functionalization, laser irradiation, antibody

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2 Nanotechnology-Based Treatment of Liver Cancer

Authors: Lucian Mocan

Abstract:

We present method of Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinomacell line), using gold nanoparticles combuned with a specific growth factor and demonstrate its selective therapeutic efficacy usig ex vivo specimens. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Ab bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of Ab bound to GNPs into tumor cells following ex-vivo intravascular perfusion. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells, gold nanoparticles, nanoparticle functionalization, laser irradiation

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1 Synthesis of 5'-Azidonucleosides as Building Blocks for the Preparation of Biologically Active Bioconjugates

Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

Abstract:

The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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