This updated review aims to describe the current status in the development of liposome-based systems for the targeted delivery of phthalocyanines for photodynamic therapy (PDT). Although a number of other drug delivery systems (DDS) can be found in the literature and have been studied for phthalocyanines or similar photosensitizers (PSs), liposomes are by far the closest to clinical practice. PDT itself finds application not only in the selective destruction of tumour tissues or the treatment of microbial infections, but above all in aesthetic medicine. From the point of view of administration, some PSs can advantageously be delivered through the skin, but for phthalocyanines, systemic administration is more suitable. However, systemic administration places higher demands on advanced DDS, active tissue targeting and reduction of side effects. This review focuses on the already described liposomal DDS for phthalocyanines, but also describes examples of DDS used for structurally related PSs, which can be assumed to be applicable to phthalocyanines as well.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Tuberous sclerosis complex (TSC), a multi-system genetic disorder often associated with autism spectrum disorder (ASD), is caused by mutations of TSC1 or TSC2, which lead to constitutive overactivation of mammalian target of rapamycin (mTOR). In several Tsc1+/- and Tsc2+/- animal models, cognitive and social behavior deficits were reversed by mTOR inhibitors. However, phase II studies have not shown amelioration of ASD and cognitive deficits in individuals with TSC during mTOR inhibitor therapy. We asked here if developmental epilepsy, common in the majority of individuals with TSC but absent in most animal models, could explain the discrepancy. METHODS: At postnatal day P12, developmental status epilepticus (DSE) was induced in male Tsc2+/- (Eker) and wild-type rats, establishing four experimental groups including controls. In adult animals (n = 36), the behavior was assessed in the paradigms of social interaction test, elevated plus-maze, light-dark test, Y-maze, and novel object recognition. The testing was carried out before medication (T1), during a 2-week treatment with the mTOR inhibitor everolimus (T2) and after an 8-week washing-out (T3). Electroencephalographic (EEG) activity was recorded in a separate set of animals (n = 18). RESULTS: Both Tsc2+/- mutation and DSE caused social behavior deficits and epileptiform EEG abnormalities (T1). Everolimus led to a persistent improvement of the social deficit induced by Tsc2+/-, while deficits related to DSE did not respond to everolimus (T2, T3). CONCLUSIONS: These findings may contribute to an explanation why ASD symptoms in individuals with TSC, where comorbid early-onset epilepsy is common, were not reliably ameliorated by mTOR inhibitors in clinical studies.
- MeSH
- autistická porucha * MeSH
- haploinsuficience MeSH
- krysa rodu rattus MeSH
- status epilepticus * MeSH
- TOR serin-threoninkinasy genetika MeSH
- tuberin genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The focus of this review is to describe the state-of-art in the development of innovative drug delivery systems for phthalocyanines as photosensitizers for photodynamic therapy (PDT). PDT is a medical treatment combining photosensitizers (PSs) activated by visible light of a specific wavelength to selectively destroy targeted cells, tumor tissues and its surrounding vasculature. In the last decades, PDT has been under intense investigation, first as a promising alternative approach for improved cancer treatment, later against microbial infection and nowadays, mainly in aesthetic medicine, against age-related degeneration. The success of PDT is restricted because of difficulties with administration and skin permeation of PSs. As PDT importance raises, there is high interest for advanced formulations and delivery systems (DDS) for PS, especially formulations based on nanotechnology. Accordingly, this review deals with the innovations pertaining to DDS for PDT as disclosed in recent patents and literature.
Pořadí vydání: první 142 stran : barevné ilustrace, ukázky formulářů ; 30 cm
Odborná kniha poskytuje základní informace z oblasti ochrany obyvatelstva v České republice včetně aktuálních bezpečnostních hrozeb, koncepcí, názorů a procedur na základě soudobých vědeckých poznatků.; Ochrana obyvatelstva je prioritní doménou krizového a havarijního plánování a řízení. Publikace je určena pro přípravu krizových manažerů.
- MeSH
- bezpečnost MeSH
- civilní obrana MeSH
- plánování postupu v případě katastrof metody MeSH
- Geografické názvy
- Česká republika MeSH
- Konspekt
- Úkoly veřejné správy, správní opatření, legislativa
- NLK Obory
- státní správa
- NLK Publikační typ
- kolektivní monografie
We report design and synthesis of set of novel anticancer agents based on caffeine-hydrazones bearing 2-hydroxyaryl- or 2-N-heteroaryl moiety. Anticancer activity evaluation using seven cancer cell lines and two non-malignant cell lines demonstrated that several derivatives display significant anticancer activity and great selectivity index toward T-lymphoblastic leukaemia cells. In general, hydrazones bearing 2-N-heteroaryl moiety are more active and selective than those with 2-hydroxyaryl moiety. Tested compounds exhibit dose-dependent inhibition of both RNA and DNA synthesis, with some exceptions. Antimicrobial activities were tested on set of twelve bacterial and yeast strains, however prepared compounds were not active, suggesting for a molecular target specific for eukaryotic cells.
- MeSH
- akutní lymfatická leukemie farmakoterapie MeSH
- antiinfekční látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- Bacteria účinky léků MeSH
- buněčné linie MeSH
- houby účinky léků MeSH
- hydrazony chemie farmakologie MeSH
- kofein chemie farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- protinádorové látky chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We report the design and synthesis of novel anticancer agents based on bis-hydrazones separated by a rigid Tröger's base skeleton. This novel approach combines a biologically active moiety (hydrazone) with this scaffold (Tröger's base) to construct DNA intercalators. Evaluation of the anticancer activity of these agents using seven cancer cell lines and two healthy cell lines found that several derivatives had potent anticancer activity and excellent selectivity indexes toward cancer cells. The antimicrobial activities were tested on a set of thirteen bacterial stains, but the prepared compounds were not active. Complexation studies using biologically important metal ions demonstrated that these compounds are able to bind Cu(2+), Fe(3+), Co(2+), Ni(2+) and Zn(2+). DNA intercalation studies showed that the compounds themselves do not interact with DNA, but their metallocomplexes do interact, most likely via intercalation into DNA.
- MeSH
- apoptóza účinky léků fyziologie MeSH
- buňky K562 MeSH
- HCT116 buňky MeSH
- hydrazony chemická syntéza farmakologie MeSH
- lidé MeSH
- preklinické hodnocení léčiv metody MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Odkud a kam kráčí farmaceutický průmysl? V posledních letech došlo k dramatickému přehodnocení cílů velkých farmaceutických společností od hledání nových látek k reinkarnaci starých molekul s novým uplatněním. Změny podmínek na trhu nutí průmysl k důslednému řízení životního cyklu léčiv. Trendy dále ukazují odklon od malých molekul k bioléčivům a sofistikované nanomedicíně. Důraz se pomalu přesouvá od pouhého léčení ke kvalitě života, od univerzálnosti k personalizované medicíně. Společnosti, které se nepřizpůsobí těmto trendům, budou čelit nejisté a znepokojivé budoucnosti.
Where from and where the pharmaceutical industry walks? In recent years there has been a dramatic reassessment of goals of large pharmaceutical companies from search for new substances to the reincarnation of the old molecules with new applications. Changes of market conditions force industry to rigorous life cycle management of pharmaceuticals. Trends also show a shift away from small molecules to biomedicine and sophisticated nanomedicine. The emphasis is slowly shifting from simply treating the quality of life, from the universality to personalized medicine. Companies that do not adapt to these trends will face an uncertain and worrying future.
- Klíčová slova
- supergenerika, nanoléčiva,
- MeSH
- farmaceutická technologie trendy MeSH
- farmaceutický průmysl * trendy MeSH
- generika * MeSH
- individualizovaná medicína MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodní články MeSH
We prepared new phases for LC that consisted of silica modified with non-covalently bonded tetrakis(β-cyclodextrin)-porphyrin (where cyclodextrin is CD) conjugates. The effects of the porphyrin core, type of spacer and β-CD moieties on the behaviours of the modified phases for the separation of aromatic compounds (benzene, toluene, ethylbenzene, propylbenzene, butylbenzene, pentylbenzene, o-terphenyl, triphenylene, phenol and caffeine) and fluorinated aromatic compounds (pentafluorobenzonitrile, pentafluoronitrobenzene and hexafluorobenzene) were studied using the Tanaka test. The results indicate that the non-covalent substitution of silica with CD-based macromolecules that have a porphyrin core can be a very effective method for preparing novel sorbents with specific chromatographic properties for applications in LC.
Metallacarborane moieties have been identified as promising pharmacophores. The pharmaceutical use of such compounds is, however, complicated by their low solubility and tendency to self-assemble in aqueous solution. In this work, we estimated the solubilities of a vast series of metallacarboranes [cobalt bis(dicarbollide) derivatives] in pure water, saline, and saline with human serum albumin as a model of blood plasma. In addition, we determined the octanol-water partition coefficients (Pow) as a lipophilicity descriptor. Pow weakly correlates with the water solubility of metallacarboranes, whereas the ability of HSA to increase the solubility of metallacarboranes correlates well with their Pow values. Because metallacarboranes are known inhibitors of HIV protease, the possible correlation between Pow and the ability to inhibit HIV protease was investigated. Results from this study indicate that interaction of metallacarborane inhibitors with HIV protease is driven by specific binding rather than by promiscuous lipophilic interactions. The most promising candidates for further drug development were identified by ligand lipophilicity efficiency analysis.
- MeSH
- inhibitory HIV-proteasy chemie farmakologie MeSH
- kobalt chemie farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- lipidy chemie MeSH
- molekulární struktura MeSH
- objevování léků MeSH
- organokovové sloučeniny chemie farmakologie MeSH
- rozpustnost MeSH
- sérový albumin chemie MeSH
- sloučeniny boru chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic boron cluster system, previously used for boron neutron capture therapy, was modified by the addition of positively charged moieties to its periphery, providing hydrophobic and nonclassical hydrogen bonding interactions with the protein. Several of these compounds show efficacy for inhibition of NO synthesis with differential effects on the various nitric oxide synthase isoforms.
- MeSH
- chemické modely MeSH
- kobalt chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- organokovové sloučeniny chemická syntéza farmakologie MeSH
- protein - isoformy MeSH
- sloučeniny boru chemická syntéza farmakologie MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
