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
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.
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
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
Cobalt bis(dicarbollide) derivatives are promising therapeutic agents however their utilization is complicated due to their low solubility and self-assembling in water. Earlier we have shown that their solubility can be increased by using of suitable biocompatible excipients--carriers of pharmaceutically active compounds. Expected mechanism of solubilization was disassembling of self-assemblies and complexation of unimers. Newly our results of time-dependent light scattering study correct this presumption. Poor solubility of all derivatives can be easily improved by using various excipients, however only heptakis(2,6-di-O-methyl)-β-cyclodextrin displays ability to disassemble self-assemblies of all derivatives and suppress their self-assembling. Surprisingly, the other excipients participate on formation of mixed assemblies of derivative/excipient complex or cover assemblies to make them more soluble without decreasing their size.
- MeSH
- biologická dostupnost MeSH
- hydrodynamika MeSH
- kobalt chemie MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- organokovové sloučeniny chemie farmakokinetika MeSH
- radiační rozptyl MeSH
- rozpustnost MeSH
- světlo MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In the field of medicinal chemistry, cobalt bis(dicarbollide) derivatives are promising therapeutic agents. The potential pharmaceutical utilization of metallacarboranes is complicated due to spontaneous self-assembling in water. This problem can be solved by using suitable deaggregating agent. We present here the comprehensive screen of substituted cobalt bis(dicarbollide) derivatives with cyclodextrin derivatives, classical surfactants and amphiphilic copolymers to find general biocompatible excipients. Preliminary results are obtained by using UV/Vis spectroscopy as the technique with the best ratio of applicable information to time and source dependence.
- MeSH
- kobalt analýza chemie MeSH
- lidé MeSH
- pomocné látky analýza chemie MeSH
- rozpustnost MeSH
- voda analýza chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Metallacarboranes and their derivatives are the recently discovered inhibitors of HIV protease. The main goal of this work was to study the interaction of parent metallacarborane derivatives with cyclodextrins (CD) differing in the inner cavity size. This interaction can improve the drug solubility and its transport to the cells. For ?-, ß- and ?-CD, NMR titrations with sodium cobalt(III) bis(1,2-dicarbollide) were performed at various CD concentrations. It was found that the greatest change in the 1H NMR chemical shift is observed at position 3 of CD on the inner broader rim of the cone-shaped molecule of CD. For ?-CD, the NMR titration curves correspond to the 1:1 stoichiometry and to the stability constant ca. 900. For ß- CD, simultaneous formation of 1:1 and 2:1 complexes and higher stability constants at least by two orders of magnitude follow from the titration curves. For ?-CD, more than two types of complexes are present. It was shown for ß- CD that the increased temperature does not significantly influence the titration curves. The model, consisting of a high number of adjustable parameters, for the determination of stability constants of the complexes must be confirmed by independent analytical methods such as isothermal calorimetry and X-ray structure determination.
