Microneedle System Coated with Hydrogels Containing Protoporphyrin IX for Potential Application in Pharmaceutical Technology.

The article aims to outline the potential of treating malignant skin cancer with microneedles covered with polymer layers containing a photosensitizer-protoporphyrin IX disodium salt (PPIX). The usefulness of stereolithography (SLA), which is a form of 3D-printing technology, for the preparation of a microneedle system with protoporphyrin IX was demonstrated. The SLA method allowed for pyramid-shaped microneedles to be printed that were covered with three different 0.1% PPIX hydrogels based on sodium alginate, xanthan, and poloxamer. Rheological tests and microscopic analysis of the hydrogels were performed. Microneedles coated with two layers of poloxamer-based hydrogel containing 0.1% PPIX were subjected to release tests in Franz diffusion cells. The release profile of PPIX initially increased and then remained relatively constant. The amount of substance released after a four-hour test in three Franz cells was 0.2569 ± 0.0683 mg/cm2. Moreover, the acute toxicity of this type of microneedle was assessed using the Microtox system. The obtained results show the usefulness of further development studies on microneedles as carriers of photosensitizing agents.

Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.

Many purine derivatives are active pharmaceutical ingredients of significant importance in the therapy of autoimmune diseases, cancers, and viral infections. In many cases, their medical use is limited due to unfavorable physicochemical and pharmacokinetic properties. These problems can be overcome by the preparation of the prodrugs of purines or by combining these compounds with nanoparticles. Herein, we aim to review the scientific progress and perspectives for polymer-based nanoparticles as drug delivery systems for purines. Polymeric nanoparticles turned out to have the potential to augment antiviral and antiproliferative effects of purine derivatives by specific binding to receptors (ASGR1-liver, macrophage mannose receptor), increase in drug retention (in eye, intestines, and vagina), and permeation (intranasal to brain delivery, PEPT1 transport of acyclovir). The most significant achievements of polymer-based nanoparticles as drug delivery systems for purines were found for tenofovir disoproxil in protection against HIV, for acyclovir against HSV, for 6-mercaptopurine in prolongation of mice ALL model life, as well as for 6-thioguanine for increased efficacy of adoptively transferred T cells. Moreover, nanocarriers were able to diminish the toxic effects of acyclovir, didanosine, cladribine, tenofovir, 6-mercaptopurine, and 6-thioguanine.

Tea-break with epigallocatechin gallate derivatives - Powerful polyphenols of great potential for medicine.

Epigallocatechin gallate (EGCG) is a polyphenol present in green tea (Camellia sinensis), which has revealed anti-cancer effects toward a variety of cancer cells in vitro and protective potential against neurodegenerative diseases such as Alzheimer's and Parkinson's. Unfortunately, EGCG presents disappointing bioavailability after oral administration, primarily due to its chemical instability and poor absorption. Due to these limitations, EGCG is currently not used in medication, but only as a dietary supplement in the form of green tea extract. Therefore, it needs further modifications before being considered suitable for extensive medical applications. In this article, we review the scientific literature about EGCG derivatives focusing on their biological properties and potential medical applications. The most common chemical modifications of epigallocatechin gallate rely on introducing fatty acid chains or sugar molecules to its chemical structure to modify solubility. Another frequently employed procedure is based on blocking EGCG's hydroxyl groups with various substituents. Novel derivatives reveal interesting properties, of which, antioxidant, anti-inflammatory, antitumor and antimicrobial, are especially important. It is worth noting that the most promising EGCG derivatives present higher stability and activity than base EGCG.

Metal Nanoparticle-Flavonoid Connections: Synthesis, Physicochemical and Biological Properties, as Well as Potential Applications in Medicine.

Flavonoids are polyphenolic compounds widely occurring throughout the plant kingdom. They are biologically active and have many medical applications. Flavonoids reveal chemopreventive, anticarcinogenic, and antioxidant properties, as well as being able to modulate the immune system response and inhibit inflammation, angiogenesis, and metastasis. Polyphenols are also believed to reverse multidrug resistance via various mechanisms, induce apoptosis, and activate cell death signals in tumor cells by modulating cell signaling pathways. The main limitation to the broader usage of flavonoids is their low solubility, poor absorption, and rapid metabolism. To tackle this, the combining of flavonoids with nanocarriers could improve their bioavailability and create systems of wider functionalities. Recently, interest in hybrid materials based on combinations of metal nanoparticles with flavonoids has increased due to their unique physicochemical and biological properties, including improved selectivity toward target sites. In addition, flavonoids have further utilities, even in the initial step of preparation of metal nanomaterials. The review offers knowledge on multiple possibilities of the synthesis of flavonoid-metal nanoparticle conjugates, as well as presents some of their features such as size, shape, surface charge, and stability. The flavonoid-metal nanoparticles are also discussed regarding their biological properties and potential medical applications.

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure-Activity Evaluation, and Biological Activity.

Curcumin has been modified in various ways to broaden its application in medicine and address its limitations. In this study, we present a series of curcumin-based derivatives obtained by replacing the hydroxy groups in the feruloyl moiety with polyethylene glycol (PEG) chains and the addition of the BF2 moiety to the carbonyl groups. Tested compounds were screened for their cytotoxic activity toward two bladder cancer cell lines, 5637 and SCaBER, and a noncancerous cell line derived from lung fibroblasts (MRC-5). Cell viability was analyzed under normoxic and hypoxic conditions (1% oxygen). Structure-activity relationships (SARs) are discussed, and curcumin derivatives equipped within feruloyl moieties with 3-methoxy and 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy} substituents (5) were selected for further analysis. Compound 5 did not affect the viability of MRC-5 cells and exerted a stronger cytotoxic effect under hypoxic conditions. However, the flow cytometry studies showed that PEGylation did not improve cellular uptake. Another observation was that the lack of serum proteins limits the intracellular uptake of curcumin derivative 5. The preliminary mechanism of action studies indicated that compound 5 under hypoxic conditions induced G2/M arrest in a dose-dependent manner and increased the expression of stress-related proteins such as p21/CIP1, phosphorylated HSP27, ADAMTS-1, and phosphorylated JNK. In summary, the results of the studies indicated that PEGylated curcumin is a more potent compound against bladder cancer cell lines than the parent compound, and derivative 5 is worthy of further investigation to clarify its mechanism of anticancer action under hypoxic conditions.

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma.

Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAP:POPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC50 equal 2.9 ± 0.9 µM after 24 hours of incubation. Noteworthy, curcumin and orientin mixture in liposomal formulation exhibited a synergistic effect against GBM. Moreover, the impact on the expression of apoptosis-associated proteins (p53 and Caspase-3) of acteoside as well as curcumin and orientin mixture, as the most potent agents, was assessed, showing nearly 40% increase as compared to control U-138 MG and T98G cells. It should be emphasized that a new and alternative method of extrusion of the studied liposomes was developed.

The Valence and Spin State Tuning of Iron(II/III) Porphyrazines with Bulky Pyrrolyl Periphery in Solution and Solid State.

Iron(III) porphyrazines containing peripheral 2,5-dimethyl-, 2-methyl-5-phenyl-, and 2,3,5-triphenyl-1H-pyrrol-1-yl substituents were synthesized and subjected to physicochemical characterization. This was accomplished by high-resolution mass spectrometry, nuclear magnetic resonance (as diamagnetic Fe(II) derivatives), HPLC purity analysis, and UV-Vis spectroscopy, accompanied by the solvation study in dichloromethane and pyridine. X-ray structure analysis was performed for a single crystal of the previously obtained 2,5-diphenyl-substituted derivative of porphyrazine complex (5d). The octahedral geometries of iron cation, present in the porphyrazine core, influenced the packing mode of molecules in the crystals. Mössbauer studies, performed for solid samples of iron porphyrazines, indicated that low-spin reduced iron states might occupy low- or high-symmetry binding sites. It was found that the hyperfine parameters and the subsequent contribution of the iron cations depend on the number of phenyl groups surrounding the pyrrolyl moiety. For iron(II) porphyrazine 2,3,5-triphenylpyrrol-1-yl substituents (5b), a high-spin ferrous state fraction was observed. Temperature-dependent measurements showed that the freed rotation of the peripheral porphyrazine ligands and the increased flexibility of the macrocycle ring result in the Fe2+ ion being stabilized in a diamagnetic state at a binding site of high symmetry at room temperature in the solid state. This process is most probably stimulated by the range of collective motions of the polymeric ribbons consisting of iron(II) porphyrazines observed in the X-ray.

Chitosan-based films with cannabis oil as a base material for wound dressing application.

This study focuses on obtaining and characterizing novel chitosan-based biomaterials containing cannabis oil to potentially promote wound healing. The primary active substance in cannabis oil is the non-psychoactive cannabidiol, which has many beneficial properties. In this study, three chitosan-based films containing different concentrations of cannabis oil were prepared. As the amount of oil increased, the obtained biomaterials became rougher as tested by atomic force microscopy. Such rough surfaces promote protein adsorption, confirmed by experiments assessing the interaction between human albumin with the obtained materials. Increased oil concentration also improved the films' mechanical parameters, swelling capacity, and hydrophilic properties, which were checked by the wetting angle measurement. On the other hand, higher oil content resulted in decreased water vapour permeability, which is essential in wound dressing. Furthermore, the prepared films were subjected to an acute toxicity test using a Microtox. Significantly, the film's increased cannabis oil content enhanced the antimicrobial effect against A. fischeri for films in direct contact with bacteria. More importantly, cell culture studies revealed that the obtained materials are biocompatible and, therefore, they might be potential candidates for application in wound dressing materials.

Role of curcumin in selected head and neck lesions. Limitations on the use of the Hep-2 cell line: A critical review.

Neoplastic diseases of the upper respiratory airways, as well as head and neck cancers, are a frequent cause of death and significantly affect the quality of life of both patients and survivors. As the frequency increases, new and improved treatment techniques are sought. Promising properties in this respect are expressed by a natural compound - curcumin. Along with its derivatives, it was found useful in the treatment of a series of cancers. Curcumin was found to be effective in clinical trials and in vitro, in vivo anticancer experiments. Nanoformulations (e.g., poly(lactide-co-glycolic acid)-based nanoparticles, nanoemulsions), and modifications of curcumin, as well as its combinations with other substances (e.g., catechins, cisplatin) or treatments (e.g., radiotherapy or local use in inhalation), were found to enhance the antitumor effect. This review aims to summarize the recent findings for the treatment of head and neck diseases, especially squamous cell carcinomas (HNSCCs), including drawing attention to the constant use of the misidentified Hep-2 cell line and proposing databases purposed at eliminating this problem. Moreover, this manuscript focuses on pointing out the molecular mechanisms of therapy that have been reached and emphasizing the shortcomings that still need to be addressed.

Liposomal Nanoformulation as a Carrier for Curcumin and pEGCG-Study on Stability and Anticancer Potential.

Nanoformulations are regarded as a promising tool to enable the efficient delivery of active pharmaceutical ingredients to the target site. One of the best-known and most studied nanoformulations are liposomes-spherical phospholipid bilayered nanocarriers resembling cell membranes. In order to assess the possible effect of a mixture of polyphenols on both the stability of the formulation and its biological activity, two compounds were embedded in the liposomes-(i) curcumin (CUR), (ii) a peracetylated derivative of (-)-epigallocatechin 3-O-gallate (pEGCG), and (iii) a combination of the aforementioned. The stability of the formulations was assessed in two different temperature ranges (4-8 and 20 °C) by monitoring both the particle size and their concentration. It was found that after 28 days of the experiment, the liposomes remained largely unchanged in terms of the particle size distribution, with the greatest change from 130 to 146 nm. The potential decomposition of the carried substances was evaluated using HPLC. The combined CUR and pEGCG was sensitive to temperature conditions; however its stability was greatly increased when compared to the solutions of the individual compounds alone-up to 9.67% of the initial concentration of pEGCG in liposomes after 28 days storage compared to complete decomposition within hours for the non-encapsulated sample. The potential of the prepared formulations was assessed in vitro on prostate (LNCaP) and bladder cancer (5637) cell lines, as well as on a non-cancerous human lung fibroblast cell line (MRC-5), with the highest activity of IC50 equal 15.33 ± 2.03 µM for the mixture of compounds towards the 5637 cell line.

Nipagin-Functionalized Porphyrazine and Phthalocyanine-Synthesis, Physicochemical Characterization and Toxicity Study after Deposition on Titanium Dioxide Nanoparticles P25.

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.

In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine.

Azulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.

Modeling the photodynamic effect in 2D versus 3D cell culture under normoxic and hypoxic conditions.

BACKGROUND: Photodynamic therapy (PDT), mainly as a combined therapy, can still be considered a promising technology for targeted cancer treatment. Besides the several and essential benefits of PDT, there are some concerns and limitations, such as complex dosimetry, tumor hypoxia, and other mechanisms of resistance. In this study, we present how the cell culture model and cell culture conditions may affect the response to PDT treatment. It was studied by applying two different 3D cell culture, non-scaffold, and hydrogel-based models under normoxic and hypoxic conditions. In parallel, a detailed mechanism of the action of zinc phthalocyanine M2TG3 was presented. METHODS: Hydrogel-based and tumor spheroids consisting of LNCaP cells, were used as 3D cell culture models in experiments performed under normoxic and hypoxic (1% of oxygen) conditions. Several analyses were performed to compare the activity of M2TG3 under different conditions, such as cytotoxicity, the level of proapoptotic and stress-related proteins, caspase activity, and antioxidant gene expression status. Additionally, we tested bioluminescence and fluorescence assays as a useful approach for a hydrogel-based 3D cell culture. RESULTS: We found that M2TG3 might lead to apoptotic cancer cell death and is strongly dependent on the model and oxygen availability. Moreover, the expression of the genes modulated in the antioxidative system in 2D and 3D cell culture models were presented. The tested bioluminescence assay revealed several advantages, such as repetitive measurements on the same sample and simultaneous analysis of different parameters due to the non-lysing nature of this assay. CONCLUSIONS: It was shown that M2TG3 can effectively cause cancer cell death via a different mechanism, depending on cell culture conditions such as the model and oxygen availability.

Role of Curcumin and (-)-Epigallocatechin-3-O-Gallate in Bladder Cancer Treatment: A Review.

The incidence of bladder cancer (BC) is increasing, and although current therapeutic approaches are effective in many cases, recurrence of BC is common. Therefore, it seems necessary to search not only for novel therapeutic approaches, but also for new therapeutic agents. Natural polyphenols, such as curcumin (CUR) and epigallocatechin gallate (EGCG), possess remarkable antitumor activity. Their biochemical mechanisms of action include regulation of signaling pathways, modeling of proteins involved in apoptosis and cell cycle inhibition, angiogenesis, and the proliferation, migration and adhesion of tumor cells. Both compounds also present antioxidant, anti-inflammatory, antibacterial and antiviral properties. CUR has been considered a promising candidate for the treatment of cystic fibrosis, Alzheimer's disease or malaria, whereas EGCG can play a supportive role in the treatment of obesity, metabolic and neurodegenerative diseases. The review summarizes the latest research on the role of CUR and EGCG in the treatment of BC. In particular, the effects of CUR and EGCG, and their prospects for use in BC therapy, their inhibition of cancer development and their prevention of multidrug resistance, are described. The literature's data indicate the possibility of achieving the effect of synergism of both polyphenols in BC therapy, which has been observed so far in the treatment of ovarian, breast and prostate cancer.

Photosensitizing potential of tailored magnetite hybrid nanoparticles functionalized with levan and zinc (II) phthalocyanine.

Phototherapies, including photodynamic therapy (PDT), have been widely used in the treatment of various diseases, especially for cancer. However, there is still a lack of effective, safe photosensitizers that would be well tolerated by patients. The combination of several methods (like phototherapy and hyperthermia) constitutes a modern therapeutic approach, which demands new materials based on components that are non-toxic without irradiation. Therefore, this study presents the synthesis and properties of novel, advanced nanomaterials in which the advantage features of the magnetic nanoparticles and photoactive compounds were combined. The primary purpose of this work was the synthesis of magnetic nanoparticles coated with biocompatible and antitumor polysaccharide - levan, previously unknown from scientific literature, and the deposition of potent photosensitizer - zinc(II) phthalocyanine on their surface. In order to better characterize the nature of the coating covering the magnetic core, the atomic force microscope analysis, a contact angle measurement, and the mechanical properties of pure levan and its blend with zinc(II) phthalocyanine films were investigated. This magnetic nanomaterial revealed the ability to generate singlet oxygen upon exposure to light. Finally, preliminary toxicity of obtained nanoparticles was tested using the Microtox® test - with and without irradiation.

Titanium Dioxide Nanoparticles: Prospects and Applications in Medicine.

Metallic and metal oxide nanoparticles (NPs), including titanium dioxide NPs, among polymeric NPs, liposomes, micelles, quantum dots, dendrimers, or fullerenes, are becoming more and more important due to their potential use in novel medical therapies. Titanium dioxide (titanium(IV) oxide, titania, TiO2) is an inorganic compound that owes its recent rise in scientific interest to photoactivity. After the illumination in aqueous media with UV light, TiO2 produces an array of reactive oxygen species (ROS). The capability to produce ROS and thus induce cell death has found application in the photodynamic therapy (PDT) for the treatment of a wide range of maladies, from psoriasis to cancer. Titanium dioxide NPs were studied as photosensitizing agents in the treatment of malignant tumors as well as in photodynamic inactivation of antibiotic-resistant bacteria. Both TiO2 NPs themselves, as well as their composites and combinations with other molecules or biomolecules, can be successfully used as photosensitizers in PDT. Moreover, various organic compounds can be grafted on TiO2 nanoparticles, leading to hybrid materials. These nanostructures can reveal increased light absorption, allowing their further use in targeted therapy in medicine. In order to improve efficient anticancer and antimicrobial therapies, many approaches utilizing titanium dioxide were tested. Results of selected studies presenting the scope of potential uses are discussed in this review.

S-seco-porphyrazine as a new member of the seco-porphyrazine family - Synthesis, characterization and photocytotoxicity against cancer cells.

An important subgroup within the porphyrazine (Pz) family constitutes seco-porphyrazines, in the chemical structure of which one pyrrole unit is opened in the oxidative process. So far, there are only limited data on N-seco- and C-seco-Pzs. Here, the synthesis of a novel member of the Pzs seco-family, represented by an S-seco-tribenzoporphyrazine analogue, 22,23-bis(4-(3,5-dibutoxycarbonylphenoxy)butylsulfanyl)tribenzo[b,g,l]-22,23-dioxo-22,23-seco-porphyrazinato magnesium(II), is reported, with moderate 34% yield. The new derivative was characterized using NMR spectroscopy, UV-Vis spectroscopy, and mass spectrometry. In the photochemical study performed following the indirect chemical method with 1,3-diphenylisobenzofuran, S-seco-Pz revealed a high singlet oxygen quantum yield of 0.27 in DMF. Potential photocytotoxicity of S-seco-Pz was assessed in vitro on three cancer cell lines - two oral squamous cell carcinoma cell lines derived from the tongue (CAL 27, HSC-3) and human cervical epithelial adenocarcinoma cells (HeLa). In the biological study, the macrocycle was tested in its free form and after loading into liposomes. It is worth noting that S-seco-Pz was found to be non-toxic in the dark, with cell viability levels over 80%. The photocytotoxic IC50 values for free S-seco-Pz were 0.61, 0.18, and 4.1 µM for CAL 27, HSC-3 and HeLa cells, respectively. Four different liposomal compositions were analyzed, and the cationic liposomes revealed the highest photokilling efficacy, with the IC50 values for CAL 27, HSC-3, and HeLa cells at 0.24, 0.25, and 0.31 µM, respectively. The results of the photocytotoxicity study indicate that the new S-seco-tribenzoporphyrazine can be considered as a potential photosensitizer in photodynamic therapy of cancer, along with the developed cationic liposomal nanocarrier.

Tribenzoporphyrazines with dendrimeric peripheral substituents and their promising photocytotoxic activity against Staphylococcus aureus.

Infectious diseases constitute a serious problem for human health and life. Although many bacterial and fungal infections can be successfully cured by commonly used antibiotics, a new threat emerges in the form of microbial resistance. For this reason, researchers try to find not only new active pharmaceutical ingredients for conventional antibiotherapy but also try to develop new strategies of microbial inactivation. Photodynamic antimicrobial chemotherapy, which relies on reactive oxygen species generated in situ in the presence of a photosensitizer and with the light of an appropriate wavelength, is one of them. Porphyrazines have been considered as potential photosensitizers for anticancer and antimicrobial photodynamic therapy. In this study, three tribenzoporphyrazines with dendrimeric peripheral substituents were subjected to in vitro antimicrobial photocytotoxicity study. One magnesium(II) tribenzoporphyrazine with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl substituents was synthesized and subjected to physicochemical characterization using NMR, UV-Vis, and mass spectrometry techniques. In photochemical studies this molecule revealed moderate singlet oxygen generation ability (ΦΔDMF = 0.12, ΦΔDMSO = 0.13). The other two magnesium(II) tribenzoporphyrazines applied in the biological study were 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl-substituted tribenzoporphyrazine and 4-[3,5-bis(benzyloxy)benzyloxy]phenyl-substituted tribenzopyrazinoporphyrazine. For the assessment, three microbial strains were chosen: Gram-positive bacteria Staphylococcus aureus ATCC 25923, Gram-negative bacteria Escherichia coli ATCC 25922, and fungal strain Candida albicans ATCC 10231. Very high activity against Staphylococcus aureus at low 10-6 M concentration was recorded for magnesium(II) tribenzoporphyrazines with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl and 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents with calculated log reductions of 4.4 and 4.8, respectively. It is worth noting that magnesium(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents revealed also 3.2 log reduction in bacterial growth at the concentration 10-7 M.

Photodynamic therapy of cancer with liposomal photosensitizers.

The photodynamic reaction involves the light-induced generation of an excited state in a photosensitizer molecule (PS), which then results in the formation of reactive oxygen species in the presence of oxygen, or a direct modification of a cellular molecule. Most PSs are porphyrinoids, which are highly lipophilic, and are administered usually in liposomes to facilitate their effective delivery to target cells. The currently available liposomal formulations are Visudyne® and Fospeg®. Novel PSs were developed and tested for their photodynamic activity against cancer cells. Several compounds were highly phototoxic to oral cancer cells both in free and liposome-encapsulated form, with nanomolar IC50 values. The lowest IC50s (7-13 nM) were obtained with a PS encapsulated in cationic liposomes.

In vitro photodynamic activity of lipid vesicles with zinc phthalocyanine derivative against Enterococcus faecalis.

Zinc(II) phthalocyanine bearing eight non-peripheral 2-propoxy substituents was subjected to physicochemical study and, after incorporation in lipid vesicles, assessed as a potential photosensitizer for antibacterial photodynamic therapy. The phthalocyanine derivative obtained in the macrocyclization reaction was characterized by MS and NMR techniques. Moreover, its chemical purity was confirmed by HPLC analysis. X-ray structural analysis revealed that overcrowding of the phthalocyanine derivative leads to a strong out-of-plane distortion of the π-system of the macrocycle core. In the UV-Vis absorption spectra of zinc(II) phthalocyanine two characteristic bands were found: the Soret (300-450 nm) and the Q band (600-800 nm). Photophysical properties of mono- and diprotonated forms of phthalocyanine derivative were studied with time-resolved fluorescence spectroscopy. Its tri- and tetraprotonated forms could not be obtained, because compound decomposes in higher acid concentrations. The presented zinc(II) phthalocyanine showed values of singlet oxygen generation ΦΔ = 0.18 and 0.16, the quantum yield of the photodecomposition ΦP = 3.06∙10-4 and 1.23∙10-5 and the quantum yield of fluorescence ΦFL = 0.005 and 0.004, designated in DMF and DMSO, respectively. For biological studies, phthalocyanine has been incorporated into modified liposome vesicles containing ethanol. In vitro bacteria photoinactivation study revealed no activity against Escherichia coli and 5.7 log reduction of the Enterococcus faecalis growth.