Anna Karewicz

Interaction of curcumin with lipid monolayers and liposomal bilayers

Curcumin shows huge potential as an anticancer and anti-inflammatory agent. However, to achieve a satisfactory bioavailability and stability of this compound, its liposomal form is preferable. Our detailed studies on the curcumin interaction with lipid membranes are aimed to obtain better understanding of the mechanism and eventually to improve the efficiency of curcumin delivery to cells. Egg yolk phosphatidylcholine (EYPC) one-component monolayers and bilayers, as well as mixed systems containing additionally dihexadecyl phosphate (DHP) and cholesterol, were studied. Curcumin binding constant to EYPC liposomes was determined based on two different methods: UV/Vis absorption and fluorescence measurements to be 4.26×10(4)M(-1) and 3.79×10(4)M(-1), respectively. The fluorescence quenching experiment revealed that curcumin locates in the hydrophobic region of EYPC liposomal bilayer. It was shown that curcumin impacts the size and stability of the liposomal carriers significantly. Loaded into the EYPC/DPH/cholesterol liposomal bilayer curcumin stabilizes the system proportionally to its content, while the EYPC/DPH system is destabilized upon drug loading. The three-component lipid composition of the liposome seems to be the most promising system for curcumin delivery. An interaction of free and liposomal curcumin with EYPC and mixed monolayers was also studied using Langmuir balance measurements. Monolayer systems were treated as a simple model of cell membrane. Condensing effect of curcumin on EYPC and EYPC/DHP monolayers and loosening influence on EYPC/DHP/chol ones were observed. It was also demonstrated that curcumin-loaded EYPC liposomes are more stable upon interaction with the model lipid membrane than the unloaded ones.

Curcumin-containing liposomes stabilized by thin layers of chitosan derivatives.

Stable vesicles for efficient curcumin encapsulation, delivery and controlled release have been obtained by coating of liposomes with thin layer of newly synthesized chitosan derivatives. Three different derivatives of chitosan were obtained and studied: the cationic (by introduction of the stable, quaternary ammonium groups), the hydrophobic (by attachment of N-dodecyl groups) and cationic-hydrophobic one (containing both quaternary ammonium and N-dodecyl groups). Zeta potential measurements confirmed effective coating of liposomes with all these chitosan derivatives. The liposomes coated with cationic-hydrophobic chitosan derivative are the most promising curcumin carriers; they can easily penetrate cell membrane and release curcumin in a controlled manner. Biological studies indicated that such systems are non-toxic for murine fibroblasts (NIH3T3) while toxic toward murine melanoma (B16F10) cell line.

Polymeric photosensitizers. Part 4. Synthesis of poly(sodium styrenesulfonate-block-N-vinylcarbazole) by nitroxide-mediated free radical polymerization

Abstract Block amphiphilic copolymer, poly(sodium styrenesulfonate- block - N -vinylcarbazole) (PSSS- block -VCz), was synthesized by nitroxide-mediated “living” free radical polymerization in homogenous solution. The procedure of the synthesis of poly(sodium styrenesulfonate) (PSSS) via the same technique was modified to reduce the amount of mediator and initiator needed. Camphorsulphonic acid (CSA) and acetic anhydride (AA) were used as rate-accelerating additives in polymerization of PSSS and PSSS- block -VCz, respectively. The physicochemical and photophysical properties of PSSS-block-VCz copolymer were determined and discussed.

Polymeric delivery systems for dexamethasone

Glucocorticoids (GCs) are broadly used in the treatment of inflammation and in suppressing hyperactivity of the immune system expressed in allergies, asthma, autoimmune diseases and sepsis. They are pleiotropic in nature, showing a wide range of diverse effects, including those which are harmful for the organism. Dexamethasone (DEX) is one of the most frequently used GCs and is considered as one of the safest. Still serious side-effects have been observed for this drug, mostly due to its hydrophobicity and low bioavailability. The potentially promising polymeric carrier systems to deliver DEX effectively are revised.

Studies of the antenna effect in polymer molecules. 29. Synthesis and properties of poly[sodium styrene sulfonate-co-(4-acryolyloxyphenyl)-10,15,20-tritolylporphyrin] in aqueous solution

Abstract The novel water soluble antenna polyelectrolyte: poly[sodium styrene sulfonate-co-(4-acryolyloxyphenyl)-10,15,20-tritolylporphyrin] (PSSS-Po) was synthesised, and its photophysical and photochemical properties were studied. Solubilisation of the various molecular probes such as pyrene or perylene in aqueous solution of the PSSS-Po proved that the polymer chain adopts the compact conformation. The interior of the polymer pseudomicelle is significantly less polar than water. The effective quenching of polymeric porphyrin fluorescence by sulfopropyl viologen (SPV) can be explained considering the possibility of electron transfer from the singlet-excited state of Po to SPV. This has been supported by measuring an absorption spectrum for PSSS-Po/SPV system after selective irradiation of Po chromophores. The formation of the new absorption bands characteristic for SPV − radical anion indicated that the charge separation was achieved in that system.

Novel polymeric inhibitors of HCoV-NL63

Abstract The human coronavirus NL63 is generally classified as a common cold pathogen, though the infection may also result in severe lower respiratory tract diseases, especially in children, patients with underlying disease, and elderly. It has been previously shown that HCoV-NL63 is also one of the most important causes of croup in children. In the current manuscript we developed a set of polymer-based compounds showing prominent anticoronaviral activity. Polymers have been recently considered as promising alternatives to small molecule inhibitors, due to their intrinsic antimicrobial properties and ability to serve as matrices for antimicrobial compounds. Most of the antimicrobial polymers show antibacterial properties, while those with antiviral activity are much less frequent. A cationically modified chitosan derivative, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and hydrophobically-modified HTCC were shown to be potent inhibitors of HCoV-NL63 replication. Furthermore, both compounds showed prominent activity against murine hepatitis virus, suggesting broader anticoronaviral activity.

A thermosensitive carrageenan-based polymer: Synthesis, characterization and interactions with a cationic surfactant

Novel polyelectrolytes were obtained by grafting N-isopropylacrylamide (NIPAM) on the ι-carrageenan (CAR) chain. Two polymers with different grafting degrees were synthesized. The polymers were found to show the lower critical solution temperature (LCST) close to that of PNIPAM. The LCST values were dependent on the concentration of salt and cationic surfactant. The interactions of CAR-graft-PNIPAM with a model cationic surfactant-dodecyltrimethyl ammonium chloride (DTAC) in water and 0.15M NaCl were studied. It was found that both ι-carrageenan and CAR-graft-PNIPAM polymers interact with DTAC. The presence of CAR-graft-PNIPAM in the solution of DTAC induces formation of surfactant aggregates at the critical aggregation concentration much lower than the cmc of the surfactant. Cac increased with ionic strength. The values of cac for CAR-graft-PNIPAM - DTAC system and standard free enthalpy changes attributed to the complexation process were determined. The results obtained for CAR-graft-PNIPAM were compared with these for the non-modified ι-carrageenan. The surfactant interactions with non-modified and grafted polymers were found to be different in nature.

Modified Polysaccharides as Versatile Materials in Controlled Delivery of Antidegenerative Agents

The mechanisms and factors causing or influencing degenerative diseases require tailor-made solutions. Natural polysaccharides are among the most versatile building units of the novel drug delivery systems. Their properties can be easily tailored to specific needs because they depend not only on the first-order structure, but also on the molecular weight, the type of end-groups and the conformation of the chain. The review presents the current state-of-art in the field of modifications of natural polysaccharides aiming at improving the delivery of anti-degenerative agents. Derivatization includes introducing of ionic or hydrophobic groups in order to adjust polarity or to obtain amphiphilic material, as well as degradable bonds, spacers and targeting moieties. The influence of the modification on the properties of the carrier, such as its size, surface charge, encapsulation efficiency, drug release profile, and stability in vivo, is discussed. Application of the polysaccharide derivatives to enhance the mucoadhesion and to actively target the drug to its site of action is also shown for a variety of carriers: nano and microparticulate systems, coated liposomes, hollow particles and polymer-drug conjugates.

Alginate-hydroxypropylcellulose hydrogel microbeads for alkaline phosphatase encapsulation

Abstract There is a growing interest in using proteins as therapeutics agents. Unfortunately, they suffer from limited stability and bioavailability. We aimed to develop a new delivery system for proteins. ALP, a model protein, was successfully encapsulated in the physically cross-linked sodium alginate/hydroxypropylcellulose (ALG-HPC) hydrogel microparticles. The obtained objects had regular, spherical shape and a diameter of ∼4 µm, as confirmed by optical microscopy and SEM analysis. The properties of the obtained microbeads could be controlled by temperature and additional coating or crosslinking procedures. The slow, sustained release of ALP in its active form with no initial burst effect was observed for chitosan-coated microspheres at pH = 7.4 and 37 °C. Activity of ALP released from ALG/HPC microspheres was confirmed by the occurance of effectively induced mineralization. SEM and AFM images revealed formation of the interpenetrated three-dimensional network of mineral, originating from the microbeads’ surfaces. FTIR and XRD analyses confirmed formation of hydroxyapatite.

Heparin--a key drug in the treatment of the circulatory degenerative diseases: controlling its action with polymers.

The properties of heparin, a key anticoagulant, are reviewed. The important issues in heparinotherapy, i.e., reaching quick anticoagulant effect, maintaining therapeutic level of anticoagulation, heparin inhibition and non-invasive heparin formulations have been reviewed and discussed, with the focus on the role of polymeric substances in the proposed solutions.